Opinion

A headline recently caught my eye about flying cars close to being a reality. Since this is pretty much the dream of everyone who grew up watching “The Jetsons,” I paused to read it.

Of course, it wasn’t quite what I hoped. Battery-powered short-range helicopter services to fly people to airports – to alleviate traffic congestion – have received Food and Drug Administration approval for testing.

In other words, they are still years away, I’m not going to be at the controls, and I won’t be taking them to my office anytime soon. (Granted, it’s only 5 minutes from my house, but wouldn’t you rather fly?)

Maybe it’s hyperbole, maybe clickbait, maybe just an enthusiastic writer, or a little of each.

On a similar note, a recent article titled, “A tiny patch may someday do your patients’ lab work,” about patches with microneedles to measure interstitial fluid, got my attention.

It certainly sounds promising, and more reasonable than the Theranos scam. This has interesting potential as a way to track lab values without repeated needle sticks.

But “someday” is the key word here. The technology is promising. For some conditions it certainly has the potential to improve patient care without frequent lab trips and blood draws.

But the point is ... it ain’t here yet. At the end of the article it says it may be available for some things within 2 years, with more indications over the next decade.

I’m not knocking the technology. That’s great news. But I’m seeing patients today. If I can’t offer it to them now, it doesn’t matter to me.

Maybe I’m a skeptic, but I’ve seen too many initially promising treatments or tests go nowhere when they move into large-scale trials. A lot of things seem like great ideas that don’t work out.

I think the microneedle patch probably has a future for certain conditions, and when it gets here it will be great for those who need it. But that won’t be tomorrow, or even 2024.

But, as with someday flying to work, I’m not holding my breath for it, either.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A headline recently caught my eye about flying cars close to being a reality. Since this is pretty much the dream of everyone who grew up watching “The Jetsons,” I paused to read it.

Of course, it wasn’t quite what I hoped. Battery-powered short-range helicopter services to fly people to airports – to alleviate traffic congestion – have received Food and Drug Administration approval for testing.

In other words, they are still years away, I’m not going to be at the controls, and I won’t be taking them to my office anytime soon. (Granted, it’s only 5 minutes from my house, but wouldn’t you rather fly?)

Maybe it’s hyperbole, maybe clickbait, maybe just an enthusiastic writer, or a little of each.

On a similar note, a recent article titled, “A tiny patch may someday do your patients’ lab work,” about patches with microneedles to measure interstitial fluid, got my attention.

It certainly sounds promising, and more reasonable than the Theranos scam. This has interesting potential as a way to track lab values without repeated needle sticks.

But “someday” is the key word here. The technology is promising. For some conditions it certainly has the potential to improve patient care without frequent lab trips and blood draws.

But the point is ... it ain’t here yet. At the end of the article it says it may be available for some things within 2 years, with more indications over the next decade.

I’m not knocking the technology. That’s great news. But I’m seeing patients today. If I can’t offer it to them now, it doesn’t matter to me.

Maybe I’m a skeptic, but I’ve seen too many initially promising treatments or tests go nowhere when they move into large-scale trials. A lot of things seem like great ideas that don’t work out.

I think the microneedle patch probably has a future for certain conditions, and when it gets here it will be great for those who need it. But that won’t be tomorrow, or even 2024.

But, as with someday flying to work, I’m not holding my breath for it, either.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A headline recently caught my eye about flying cars close to being a reality. Since this is pretty much the dream of everyone who grew up watching “The Jetsons,” I paused to read it.

Of course, it wasn’t quite what I hoped. Battery-powered short-range helicopter services to fly people to airports – to alleviate traffic congestion – have received Food and Drug Administration approval for testing.

In other words, they are still years away, I’m not going to be at the controls, and I won’t be taking them to my office anytime soon. (Granted, it’s only 5 minutes from my house, but wouldn’t you rather fly?)

Maybe it’s hyperbole, maybe clickbait, maybe just an enthusiastic writer, or a little of each.

On a similar note, a recent article titled, “A tiny patch may someday do your patients’ lab work,” about patches with microneedles to measure interstitial fluid, got my attention.

It certainly sounds promising, and more reasonable than the Theranos scam. This has interesting potential as a way to track lab values without repeated needle sticks.

But “someday” is the key word here. The technology is promising. For some conditions it certainly has the potential to improve patient care without frequent lab trips and blood draws.

But the point is ... it ain’t here yet. At the end of the article it says it may be available for some things within 2 years, with more indications over the next decade.

I’m not knocking the technology. That’s great news. But I’m seeing patients today. If I can’t offer it to them now, it doesn’t matter to me.

Maybe I’m a skeptic, but I’ve seen too many initially promising treatments or tests go nowhere when they move into large-scale trials. A lot of things seem like great ideas that don’t work out.

I think the microneedle patch probably has a future for certain conditions, and when it gets here it will be great for those who need it. But that won’t be tomorrow, or even 2024.

But, as with someday flying to work, I’m not holding my breath for it, either.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.

I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).

During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.

LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.

Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.

However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.

Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.

Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.

I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.

I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.

The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.

Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.

In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.

A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.

I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.

OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.

PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.

So, the future appears very bright for oral GLP-1 agonists. I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.

However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.

One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.

On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.

This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.

Using this approach for obesity management might help the sustainability of health care systems.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.

I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).

During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.

LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.

Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.

However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.

Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.

Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.

I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.

I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.

The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.

Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.

In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.

A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.

I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.

OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.

PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.

So, the future appears very bright for oral GLP-1 agonists. I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.

However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.

One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.

On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.

This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.

Using this approach for obesity management might help the sustainability of health care systems.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.

A version of this article first appeared on Medscape.com.

The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.

I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).

During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.

LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.

Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.

However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.

Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.

Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.

I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.

I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.

The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.

Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.

In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.

A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.

I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.

OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.

PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.

So, the future appears very bright for oral GLP-1 agonists. I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.

However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.

One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.

On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.

This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.

Using this approach for obesity management might help the sustainability of health care systems.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.

A version of this article first appeared on Medscape.com.

As a gastroenterology and hepatology fellow, choosing a career path was a daunting prospect. Despite the additional specialization, there seemed to be endless career options to consider. Did I want to join an academic, private, or hybrid practice? Should I subspecialize within the field? Was it important to incorporate research or teaching into my practice? What about opportunities to take on administrative or leadership roles?

Fellowship training at a large academic research institution provided me the opportunity to work with expert faculty in inflammatory bowel disease, esophageal disease, motility and functional gastrointestinal disease, pancreaticobiliary disease, and hepatology. I enjoyed seeing patients in each of these subspecialty clinics. But, by the end of my second year of GI fellowship, I still wasn’t sure what I wanted to do professionally.

A career in academic general gastroenterology seemed to be a good fit for my personality and goals. Rather than focusing on research, I chose to position myself as a clinician educator. I knew that having a subspecialty area of expertise would help improve my clinical practice and make me a more attractive candidate to academic centers. To help narrow my choice, I looked at the clinical enterprise at our institution and assessed where the unmet clinical needs were most acute. Simultaneously, I identified potential mentors to support and guide me through the transition from fellow to independent practitioner. I decided to focus on acquiring the skills to care for patients with anorectal diseases and lower-GI motility disorders, as this area met both of my criteria – excellent mentorship and an unmet clinical need. Under the guidance of Dr. Yolanda Scarlett, I spent my 3rd year in clinic learning to interpret anorectal manometry tests, defecograms, and sitz marker studies and treating patients with refractory constipation, fecal incontinence, and anal fissures.

With a plan to develop an expertise in anorectal diseases and low-GI motility disorders, I also wanted to focus on improving my endoscopic skills to graduate as well rounded a clinician as possible. To achieve this goal, I sought out a separate endoscopy mentor, Dr. Ian Grimm, the director of endoscopy at the University of North Carolina at Chapel Hill. Dr. Grimm, a classically trained advanced endoscopist performing endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP), had a burgeoning interest in endoscopic mucosal resection (EMR) and had just returned from a few months in Japan learning to perform endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM).

When I began working with Dr. Grimm, I had not even heard the term third-space endoscopy and knew nothing about ESD or POEM. I spent as much time as possible watching and assisting Dr. Grimm with complex endoscopic mucosal resection (EMR) during the first few months of my 3rd year. Soon after my exposure to advanced endoscopic resection, it was clear that I wanted to learn and incorporate this into my clinical practice. I watched Dr. Grimm perform the first POEM at UNC in the fall of 2016 and by that time I was hooked on learning third-space endoscopy. I observed and assisted with as many EMR, ESD, and POEM cases as I could that year. In addition to the hands-on and cognitive training with Dr. Grimm, I attended national meetings and workshops focused on learning third-space endoscopy. In the spring of my 3rd year I was honored to be the first fellow to complete the Olympus master class in ESD – a 2-day hands-on training course sponsored by Olympus. By the end of that year, I was performing complex EMR with minimal assistance and had completed multiple ESDs and POEMs with cognitive supervision only.

After fellowship, I joined the UNC faculty as a general gastroenterologist with expertise in anorectal disease and lower-GI motility disorders. While I was comfortable performing complex EMR, I still needed additional training and supervision before I felt ready to independently perform ESD or POEM. With the gracious support and encouragement of our division chief, I continued third-space endoscopy training with Dr. Grimm during dedicated protected time 2 days each month. Over the ensuing 4 years, I transitioned to fully independent practice performing all types of advanced EMR and third-space endoscopy including complex EMR, ESD, endoscopic full-thickness resection (EFTR), submucosal tunnel endoscopic resection (STER), esophageal POEM, gastric POEM, and Zenker’s POEM.

As one of the first gastroenterologists in the United States to perform third-space endoscopy without any formal training in advanced pancreaticobiliary endoscopy, I believe learning advanced endoscopic resection and third-space endoscopy is best achieved through a training pathway separate from the conventional advanced endoscopy fellowship focused on teaching EUS and ERCP. Although there are transferable skills learned from EUS and ERCP to the techniques used in third-space endoscopy, there is nothing inherent to performing EUS or ERCP that enables one to learn how to perform an ESD or a POEM.

There is a robust training pathway to teach advanced pancreaticobiliary endoscopy, but no formal training pathway exists to teach third-space endoscopy in the United States. Historically, a small number of interested and motivated advanced pancreaticobiliary endoscopists sought out opportunities to learn third-space endoscopy after completion of their advanced endoscopy fellowship, in some cases many years after graduation. For these early adopters in the United States, the only training opportunities required travel to Japan or another Eastern country with arrangements made to observe and participate in third-space endoscopy cases with experts there. With increased recognition of the benefits of ESD and POEM over the past 5-10 years in the United States, there has been greater adoption of third-space endoscopy and with it, more training opportunities. Still, there are very few institutions with formalized training programs in advanced endoscopic resection and third-space endoscopy in the United States to date.
 

Proof that this model works

In Eastern countries such as Japan, training endoscopists to perform ESD and POEM has been successfully achieved through an apprenticeship model whereby an expert in third-space endoscopy closely supervises a trainee who gains greater autonomy with increasing experience and skill over time. My personal experience is proof that this model works. But, adopting such a model more widely in the United States may prove difficult. We lack a sufficient number of experienced third-space endoscopy operators and, given the challenges to appropriate reimbursement for third-space endoscopy in the United States, there is understandable resistance to accepting the prolonged training period necessary for technical mastery of this skill.

In part, a long training period is needed because of a relative paucity of appropriate target lesions for ESD and the rarity of achalasia in the United States. While there is consensus among experts regarding the benefits of ESD for resection of early gastric cancer (EGC), relatively few EGCs are found in the United States and indications for ESD outside resection of EGC are less well defined with less clear benefits over more widely performed piecemeal EMR. Despite these challenges, it is critical that we continue to develop dedicated training pathways to teach advanced endoscopic resection and third-space endoscopy in the United States. My practice has evolved considerably since completion of fellowship nearly 6 years ago, and I now focus almost exclusively on advanced endoscopic resection and third-space endoscopy. Recently, Dr. Grimm and I began an advanced endoscopic resection elective for the general GI fellows at UNC and we are excited to welcome our first advanced endoscopic resection and third-space endoscopy fellow to UNC this July.

While there are many possible avenues to expertise in advanced endoscopic resection, few will likely follow the same path that I have taken. Trainees who are interested in pursuing this subspecialty should seek out supportive mentors in a setting where there is already a robust case volume of esophageal motility disorders and endoscopic resections. Success requires the persistent motivation to seek out diverse opportunities for self-study, exposure to experts, data on developments in the field, and hands-on exposure to as many ex-vivo and in-vivo cases as possible.

Dr. Kroch is assistant professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. He disclosed having no conflicts of interest.

As a gastroenterology and hepatology fellow, choosing a career path was a daunting prospect. Despite the additional specialization, there seemed to be endless career options to consider. Did I want to join an academic, private, or hybrid practice? Should I subspecialize within the field? Was it important to incorporate research or teaching into my practice? What about opportunities to take on administrative or leadership roles?

Fellowship training at a large academic research institution provided me the opportunity to work with expert faculty in inflammatory bowel disease, esophageal disease, motility and functional gastrointestinal disease, pancreaticobiliary disease, and hepatology. I enjoyed seeing patients in each of these subspecialty clinics. But, by the end of my second year of GI fellowship, I still wasn’t sure what I wanted to do professionally.

A career in academic general gastroenterology seemed to be a good fit for my personality and goals. Rather than focusing on research, I chose to position myself as a clinician educator. I knew that having a subspecialty area of expertise would help improve my clinical practice and make me a more attractive candidate to academic centers. To help narrow my choice, I looked at the clinical enterprise at our institution and assessed where the unmet clinical needs were most acute. Simultaneously, I identified potential mentors to support and guide me through the transition from fellow to independent practitioner. I decided to focus on acquiring the skills to care for patients with anorectal diseases and lower-GI motility disorders, as this area met both of my criteria – excellent mentorship and an unmet clinical need. Under the guidance of Dr. Yolanda Scarlett, I spent my 3rd year in clinic learning to interpret anorectal manometry tests, defecograms, and sitz marker studies and treating patients with refractory constipation, fecal incontinence, and anal fissures.

With a plan to develop an expertise in anorectal diseases and low-GI motility disorders, I also wanted to focus on improving my endoscopic skills to graduate as well rounded a clinician as possible. To achieve this goal, I sought out a separate endoscopy mentor, Dr. Ian Grimm, the director of endoscopy at the University of North Carolina at Chapel Hill. Dr. Grimm, a classically trained advanced endoscopist performing endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP), had a burgeoning interest in endoscopic mucosal resection (EMR) and had just returned from a few months in Japan learning to perform endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM).

When I began working with Dr. Grimm, I had not even heard the term third-space endoscopy and knew nothing about ESD or POEM. I spent as much time as possible watching and assisting Dr. Grimm with complex endoscopic mucosal resection (EMR) during the first few months of my 3rd year. Soon after my exposure to advanced endoscopic resection, it was clear that I wanted to learn and incorporate this into my clinical practice. I watched Dr. Grimm perform the first POEM at UNC in the fall of 2016 and by that time I was hooked on learning third-space endoscopy. I observed and assisted with as many EMR, ESD, and POEM cases as I could that year. In addition to the hands-on and cognitive training with Dr. Grimm, I attended national meetings and workshops focused on learning third-space endoscopy. In the spring of my 3rd year I was honored to be the first fellow to complete the Olympus master class in ESD – a 2-day hands-on training course sponsored by Olympus. By the end of that year, I was performing complex EMR with minimal assistance and had completed multiple ESDs and POEMs with cognitive supervision only.

After fellowship, I joined the UNC faculty as a general gastroenterologist with expertise in anorectal disease and lower-GI motility disorders. While I was comfortable performing complex EMR, I still needed additional training and supervision before I felt ready to independently perform ESD or POEM. With the gracious support and encouragement of our division chief, I continued third-space endoscopy training with Dr. Grimm during dedicated protected time 2 days each month. Over the ensuing 4 years, I transitioned to fully independent practice performing all types of advanced EMR and third-space endoscopy including complex EMR, ESD, endoscopic full-thickness resection (EFTR), submucosal tunnel endoscopic resection (STER), esophageal POEM, gastric POEM, and Zenker’s POEM.

As one of the first gastroenterologists in the United States to perform third-space endoscopy without any formal training in advanced pancreaticobiliary endoscopy, I believe learning advanced endoscopic resection and third-space endoscopy is best achieved through a training pathway separate from the conventional advanced endoscopy fellowship focused on teaching EUS and ERCP. Although there are transferable skills learned from EUS and ERCP to the techniques used in third-space endoscopy, there is nothing inherent to performing EUS or ERCP that enables one to learn how to perform an ESD or a POEM.

There is a robust training pathway to teach advanced pancreaticobiliary endoscopy, but no formal training pathway exists to teach third-space endoscopy in the United States. Historically, a small number of interested and motivated advanced pancreaticobiliary endoscopists sought out opportunities to learn third-space endoscopy after completion of their advanced endoscopy fellowship, in some cases many years after graduation. For these early adopters in the United States, the only training opportunities required travel to Japan or another Eastern country with arrangements made to observe and participate in third-space endoscopy cases with experts there. With increased recognition of the benefits of ESD and POEM over the past 5-10 years in the United States, there has been greater adoption of third-space endoscopy and with it, more training opportunities. Still, there are very few institutions with formalized training programs in advanced endoscopic resection and third-space endoscopy in the United States to date.
 

Proof that this model works

In Eastern countries such as Japan, training endoscopists to perform ESD and POEM has been successfully achieved through an apprenticeship model whereby an expert in third-space endoscopy closely supervises a trainee who gains greater autonomy with increasing experience and skill over time. My personal experience is proof that this model works. But, adopting such a model more widely in the United States may prove difficult. We lack a sufficient number of experienced third-space endoscopy operators and, given the challenges to appropriate reimbursement for third-space endoscopy in the United States, there is understandable resistance to accepting the prolonged training period necessary for technical mastery of this skill.

In part, a long training period is needed because of a relative paucity of appropriate target lesions for ESD and the rarity of achalasia in the United States. While there is consensus among experts regarding the benefits of ESD for resection of early gastric cancer (EGC), relatively few EGCs are found in the United States and indications for ESD outside resection of EGC are less well defined with less clear benefits over more widely performed piecemeal EMR. Despite these challenges, it is critical that we continue to develop dedicated training pathways to teach advanced endoscopic resection and third-space endoscopy in the United States. My practice has evolved considerably since completion of fellowship nearly 6 years ago, and I now focus almost exclusively on advanced endoscopic resection and third-space endoscopy. Recently, Dr. Grimm and I began an advanced endoscopic resection elective for the general GI fellows at UNC and we are excited to welcome our first advanced endoscopic resection and third-space endoscopy fellow to UNC this July.

While there are many possible avenues to expertise in advanced endoscopic resection, few will likely follow the same path that I have taken. Trainees who are interested in pursuing this subspecialty should seek out supportive mentors in a setting where there is already a robust case volume of esophageal motility disorders and endoscopic resections. Success requires the persistent motivation to seek out diverse opportunities for self-study, exposure to experts, data on developments in the field, and hands-on exposure to as many ex-vivo and in-vivo cases as possible.

Dr. Kroch is assistant professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. He disclosed having no conflicts of interest.

As a gastroenterology and hepatology fellow, choosing a career path was a daunting prospect. Despite the additional specialization, there seemed to be endless career options to consider. Did I want to join an academic, private, or hybrid practice? Should I subspecialize within the field? Was it important to incorporate research or teaching into my practice? What about opportunities to take on administrative or leadership roles?

Fellowship training at a large academic research institution provided me the opportunity to work with expert faculty in inflammatory bowel disease, esophageal disease, motility and functional gastrointestinal disease, pancreaticobiliary disease, and hepatology. I enjoyed seeing patients in each of these subspecialty clinics. But, by the end of my second year of GI fellowship, I still wasn’t sure what I wanted to do professionally.

A career in academic general gastroenterology seemed to be a good fit for my personality and goals. Rather than focusing on research, I chose to position myself as a clinician educator. I knew that having a subspecialty area of expertise would help improve my clinical practice and make me a more attractive candidate to academic centers. To help narrow my choice, I looked at the clinical enterprise at our institution and assessed where the unmet clinical needs were most acute. Simultaneously, I identified potential mentors to support and guide me through the transition from fellow to independent practitioner. I decided to focus on acquiring the skills to care for patients with anorectal diseases and lower-GI motility disorders, as this area met both of my criteria – excellent mentorship and an unmet clinical need. Under the guidance of Dr. Yolanda Scarlett, I spent my 3rd year in clinic learning to interpret anorectal manometry tests, defecograms, and sitz marker studies and treating patients with refractory constipation, fecal incontinence, and anal fissures.

With a plan to develop an expertise in anorectal diseases and low-GI motility disorders, I also wanted to focus on improving my endoscopic skills to graduate as well rounded a clinician as possible. To achieve this goal, I sought out a separate endoscopy mentor, Dr. Ian Grimm, the director of endoscopy at the University of North Carolina at Chapel Hill. Dr. Grimm, a classically trained advanced endoscopist performing endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP), had a burgeoning interest in endoscopic mucosal resection (EMR) and had just returned from a few months in Japan learning to perform endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM).

When I began working with Dr. Grimm, I had not even heard the term third-space endoscopy and knew nothing about ESD or POEM. I spent as much time as possible watching and assisting Dr. Grimm with complex endoscopic mucosal resection (EMR) during the first few months of my 3rd year. Soon after my exposure to advanced endoscopic resection, it was clear that I wanted to learn and incorporate this into my clinical practice. I watched Dr. Grimm perform the first POEM at UNC in the fall of 2016 and by that time I was hooked on learning third-space endoscopy. I observed and assisted with as many EMR, ESD, and POEM cases as I could that year. In addition to the hands-on and cognitive training with Dr. Grimm, I attended national meetings and workshops focused on learning third-space endoscopy. In the spring of my 3rd year I was honored to be the first fellow to complete the Olympus master class in ESD – a 2-day hands-on training course sponsored by Olympus. By the end of that year, I was performing complex EMR with minimal assistance and had completed multiple ESDs and POEMs with cognitive supervision only.

After fellowship, I joined the UNC faculty as a general gastroenterologist with expertise in anorectal disease and lower-GI motility disorders. While I was comfortable performing complex EMR, I still needed additional training and supervision before I felt ready to independently perform ESD or POEM. With the gracious support and encouragement of our division chief, I continued third-space endoscopy training with Dr. Grimm during dedicated protected time 2 days each month. Over the ensuing 4 years, I transitioned to fully independent practice performing all types of advanced EMR and third-space endoscopy including complex EMR, ESD, endoscopic full-thickness resection (EFTR), submucosal tunnel endoscopic resection (STER), esophageal POEM, gastric POEM, and Zenker’s POEM.

As one of the first gastroenterologists in the United States to perform third-space endoscopy without any formal training in advanced pancreaticobiliary endoscopy, I believe learning advanced endoscopic resection and third-space endoscopy is best achieved through a training pathway separate from the conventional advanced endoscopy fellowship focused on teaching EUS and ERCP. Although there are transferable skills learned from EUS and ERCP to the techniques used in third-space endoscopy, there is nothing inherent to performing EUS or ERCP that enables one to learn how to perform an ESD or a POEM.

There is a robust training pathway to teach advanced pancreaticobiliary endoscopy, but no formal training pathway exists to teach third-space endoscopy in the United States. Historically, a small number of interested and motivated advanced pancreaticobiliary endoscopists sought out opportunities to learn third-space endoscopy after completion of their advanced endoscopy fellowship, in some cases many years after graduation. For these early adopters in the United States, the only training opportunities required travel to Japan or another Eastern country with arrangements made to observe and participate in third-space endoscopy cases with experts there. With increased recognition of the benefits of ESD and POEM over the past 5-10 years in the United States, there has been greater adoption of third-space endoscopy and with it, more training opportunities. Still, there are very few institutions with formalized training programs in advanced endoscopic resection and third-space endoscopy in the United States to date.
 

Proof that this model works

In Eastern countries such as Japan, training endoscopists to perform ESD and POEM has been successfully achieved through an apprenticeship model whereby an expert in third-space endoscopy closely supervises a trainee who gains greater autonomy with increasing experience and skill over time. My personal experience is proof that this model works. But, adopting such a model more widely in the United States may prove difficult. We lack a sufficient number of experienced third-space endoscopy operators and, given the challenges to appropriate reimbursement for third-space endoscopy in the United States, there is understandable resistance to accepting the prolonged training period necessary for technical mastery of this skill.

In part, a long training period is needed because of a relative paucity of appropriate target lesions for ESD and the rarity of achalasia in the United States. While there is consensus among experts regarding the benefits of ESD for resection of early gastric cancer (EGC), relatively few EGCs are found in the United States and indications for ESD outside resection of EGC are less well defined with less clear benefits over more widely performed piecemeal EMR. Despite these challenges, it is critical that we continue to develop dedicated training pathways to teach advanced endoscopic resection and third-space endoscopy in the United States. My practice has evolved considerably since completion of fellowship nearly 6 years ago, and I now focus almost exclusively on advanced endoscopic resection and third-space endoscopy. Recently, Dr. Grimm and I began an advanced endoscopic resection elective for the general GI fellows at UNC and we are excited to welcome our first advanced endoscopic resection and third-space endoscopy fellow to UNC this July.

While there are many possible avenues to expertise in advanced endoscopic resection, few will likely follow the same path that I have taken. Trainees who are interested in pursuing this subspecialty should seek out supportive mentors in a setting where there is already a robust case volume of esophageal motility disorders and endoscopic resections. Success requires the persistent motivation to seek out diverse opportunities for self-study, exposure to experts, data on developments in the field, and hands-on exposure to as many ex-vivo and in-vivo cases as possible.

Dr. Kroch is assistant professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. He disclosed having no conflicts of interest.

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.

For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.

In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.

I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.

There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.

Just as I was about to make a run for it, I heard: BOOM!

It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.

I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.

I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”

I yelled, “What’s going on?”

“Four people were just struck by lightning,” he said as he zoomed past.

I thought: “Sh*t. I have to go back.”

It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”

The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.

I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.

More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”

I told some agents to go find an AED, because these people needed to be shocked.

After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.

It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.

Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?

The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.

EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.

The whole experience had taken 14 minutes.

At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.

But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.

I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”

I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.

I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.

I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.

I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.

It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?

Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.

A version of this article first appeared on Medscape.com.

It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.

I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.

There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.

Just as I was about to make a run for it, I heard: BOOM!

It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.

I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.

I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”

I yelled, “What’s going on?”

“Four people were just struck by lightning,” he said as he zoomed past.

I thought: “Sh*t. I have to go back.”

It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”

The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.

I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.

More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”

I told some agents to go find an AED, because these people needed to be shocked.

After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.

It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.

Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?

The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.

EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.

The whole experience had taken 14 minutes.

At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.

But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.

I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”

I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.

I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.

I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.

I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.

It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?

Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.

A version of this article first appeared on Medscape.com.

It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.

I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.

There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.

Just as I was about to make a run for it, I heard: BOOM!

It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.

I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.

I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”

I yelled, “What’s going on?”

“Four people were just struck by lightning,” he said as he zoomed past.

I thought: “Sh*t. I have to go back.”

It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”

The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.

I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.

More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”

I told some agents to go find an AED, because these people needed to be shocked.

After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.

It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.

Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?

The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.

EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.

The whole experience had taken 14 minutes.

At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.

But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.

I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”

I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.

I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.

I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.

I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.

It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?

Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.

A version of this article first appeared on Medscape.com.

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The word “regulations” gets a mixed response. Some see regulations as necessary to protect public safety, while others argue that they block innovation, success, and profits.

This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.

I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.

Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.

But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.

Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.

This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.

This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.

I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.

But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.

But people are far from perfect. And the consequences can be terrible.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The word “regulations” gets a mixed response. Some see regulations as necessary to protect public safety, while others argue that they block innovation, success, and profits.

This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.

I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.

Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.

But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.

Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.

This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.

This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.

I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.

But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.

But people are far from perfect. And the consequences can be terrible.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The word “regulations” gets a mixed response. Some see regulations as necessary to protect public safety, while others argue that they block innovation, success, and profits.

This is common in all industries, and certainly pharmaceuticals. On any given day there are stories on industry news sites about disputes between companies and regulatory agencies.

I’d agree that some regulation is needed. The history of pharmacy has had both remarkable successes – and failures.

Let’s look at migraines, since that’s in my field. The calcitonin gene-related peptide (CGRP) drugs have been a remarkable breakthrough, certainly the biggest one since the triptans in 1992. There are currently seven on the market for both prevention and abortive use. They’re effective and (to date) pretty safe.

But it wasn’t always that way. Look back just 14 years ago to 2009, when the first promising CGRP agent (MK-3207) had its development halted because of hepatic abnormalities. It’s cousin telcagepant (MK-0974) came to a similar end 2 years later.

Without regulations in place (and the potential for lawsuits) these might have made it to market, bringing migraine relief to some and potentially serious liver damage to others. So Merck made the right decision to axe them. Researchers learned from the experience, went back to the drawing board, and developed the current generation of far-safer drugs.

This came into sharp focus in another industry recently, when the eyes of the world were on the north Atlantic. A small tourist submarine imploded and killed five people. During the inevitable media coverage it came out that the submarine hadn’t been certified for safety by any of the agencies that handle such things, falling into a gray area in international waters where inspections aren’t required.

This isn’t to say it wasn’t safe – it had made several dives before – but obviously not safe enough. While I didn’t know the late Stockton Rush (the owner/designer) it sounds like he viewed regulations as stifling innovation, and in one interview said “at some point, safety is just pure waste.” He ignored warnings from several sides about the submersible’s ability to handle deep ocean pressure and the inevitable wear and tear repeated dives will have on the hull.

I understand there’s a margin of luck, too. Bad things can happen to any of us – or any company. Some things can’t be clearly foreseen. Some drugs don’t start to show problems until they’re on the market and reach a certain number of prescriptions.

But there’s a reason we have regulations. Pretty much every government has, going back to the Roman Empire, covering numerous things. In a perfect world we wouldn’t need them.

But people are far from perfect. And the consequences can be terrible.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

A version of this article first appeared on Medscape.com.

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

A version of this article first appeared on Medscape.com.

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.

In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.

In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.

Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.

I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.

One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.

Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.

In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.

In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.

In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.

In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.

Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.

I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.

One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.

Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.

In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.

In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Those of us in the field of diabetes have long wanted to cure type 1 diabetes, and there are little steps making me feel like this might be a possibility. One of those steps is that a company named Vertex – I’m actually on the steering committee for Vertex in terms of this project – has made beta cells from stem cells. Now, instead of waiting for a cadaveric donor, we can make little beta cells. They started giving them to people in human trials. The Food and Drug Administration has been cautious because it’s new, and I get that.

In the first part of these trials, we could only give half a dose of these beta cells. The doses were determined based on what we know from giving beta-cell transplants from cadaveric donors. We gave half a dose of these stem cell–derived beta cells to two people who were having episodes of severe hypoglycemia.

In patient 1, these beta cells worked incredibly well. He became insulin independent, and now after over a year, he’s basically free of his type 1 diabetes. Patient 2 received half a dose, and she did get some activity of the beta cells, but not enough to achieve insulin independence, so she got a second dose. Shortly after the second dose, she decided she didn’t want to participate in the trial anymore and she was lost to follow-up.

Patient 2 didn’t get the same response as patient 1, but then we moved on to four more patients who got a full dose to start with. Now, there’s a total of six patients. Of those additional four patients, one of them has now been followed for a year. Just like patient 1, he’s off insulin. It’s as though his body has normal beta cells and he’s doing great. For the next three patients, we don’t have enough follow-up data to tell you what’s going to happen to them at a year.

I can tell you that, in all six patients, the beta cells worked. They basically were producing insulin, they had positive C-peptide levels, and it showed that these beta cells work when given to human beings. Now the trial is going to start giving more patients these stem cell–derived beta cells.

One of the things that’s important to realize is that this is a very small sample size, at just six individuals. Even within those six individuals, there was variation in terms of the response to the treatment. Probably, just like with all things in medicine, there will be different doses, different ways in which people do respond, people who get off of insulin completely, and people who may require some ongoing insulin therapy. I have no idea what this is going to look like as we test this in more people.

Everybody did start making C-peptide, they were having an effect of these beta cells, and it was working. We’ll have to see how well it works, how well it works in whom, and how we’re going to be able to use these types of therapies in the future.

In terms of side effects, they were really related to immunosuppression. There were no real surprises, but again, this is a very small sample size.

In summary, I think this is really hopeful. I don’t like to give false hope, but each step of this development process has shown that these beta cells derived from stem cells do seem to work in human beings as native beta cells might. Hopefully, this portends a future of newer therapies in the treatment of people with type 1 diabetes. Thank you.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

A version of this article originally appeared on Medscape.com.