25 years of chickenpox vaccine: 91 million cases prevented

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WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

 

 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

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WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

 

 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

 

WASHINGTON – In the 25 years since the United States first launched its universal vaccinations program to protect children against chickenpox (varicella), the program has seen dramatic results, a data analysis indicates.

Results from 1995 – when universal vaccinations began – through 2019 were presented an annual scientific meeting on infectious diseases by Mona Marin, MD, a medical epidemiologist at the Centers for Disease Control and Prevention. Researchers analyzed published data and surveillance data reported to the CDC.
 

Deaths in under-20 group all but eliminated

It’s now rare for children to be hospitalized with chickenpox, and deaths from the infection in people younger than 20 have largely been eliminated. But benefits extend even further.

Immunocompromised people or pregnant women and infants too young to be vaccinated also benefited from the children’s immunizations.

Each year, about 3.8 million cases, 10,500 hospitalizations, and 100 deaths from chickenpox are prevented in the United States thanks to the vaccination program, Dr. Marin said.

Over 25 years, 91 million cases, 238,000 hospitalizations, and 1,933 – 2,446 deaths have been prevented.

However, chickenpox is still widespread in most of the world.
 

U.S. first with universal program

The disease was thought to be of little consequence, Dr. Marin said, until the mid-1950s after the first cases of fatal varicella in immunocompromised children revealed the virus’ lethal potential.

The United States was the first country to introduce a universal vaccination program, Dr. Marin said. At the time, it was a one-dose vaccine. Within the first 10 years of the one-dose program, declines in chickenpox cases, hospitalization, and death rates went from 71% to 90% in comparison with previous years. But health care leaders wanted to close the remaining gap and target transmission in schools.

“It was a burden the United States considered unacceptable,” Dr. Marin said.

The leaders had seen the control of measles and polio and wanted the same for chickenpox.
 

Two-dose vaccines started in 2007

In 2007, the current two-dose policy was introduced. Administration of the first dose is recommended at age 12–15 months, and the second at age 4–6 years. Vaccination is required before the children enter kindergarten.

Coverage was high – at least 90% – the study authors reported; the two-dose program further reduced the number, size, and duration of outbreaks. Over the 25 years, the proportion of outbreaks with fewer than 10 cases increased from 28% to 73%.

By 2019, incidence had dropped by 97%, hospitalizations were down by 94%, and deaths had dropped by 97%.

The biggest decline was seen in those younger than 20, who were born during the vaccination program. That group saw declines of 97% to 99% in cases, hospitalizations, and incidence compared with rates before vaccinations.

Dr. Marin says one dose of the vaccine is moderately effective in preventing all varicella (82%) and is highly effective in preventing severe varicella (more than 97%).

“The second dose adds 10% or more improved protection against all varicella,” she said.

But there have been gains beyond medical advances.

Researchers calculated the economic benefit and found a net savings of $23 billion in medical costs (which also factored in lost wages from parents staying home to care for sick children).
 

 

 

Jaw-dropping results

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that “as someone who is not a vaccinologist, the declines in deaths, let alone hospitalizations, were jaw-dropping. I hadn’t really seen a synthesis of the impact of one and two doses.”

She said the declines in zoster among young people were interesting. The big question, she said, is what impact this may have for shingles infections in middle-aged adults over time, since chickenpox and shingles are caused by the same virus.

Dr. Marrazzo also noted the economic savings calculations.

“It’s such a cheap intervention. It’s one of the best examples of how a simple vaccine can affect a cascade of events that are a result of chronic viral infection,” she said.

There are also messages for the current debates over COVID-19 vaccinations.

“For me, it is further evidence of the profound population-level effect safe vaccines can have,” Dr. Marrazzo said.

The authors and Dr. Marrazzo report no relevant financial relationships.

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

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Lower serum bile acid levels independently predict adverse renal outcomes in T2DM and DKD

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Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

 

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

 

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

 

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

 

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

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Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

 

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

 

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

 

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

 

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

 

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

 

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

 

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

 

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

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No increase in risk for major adverse limb events with SGLT-2i vs. GLP-1RA in T2DM

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Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

 

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

 

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

 

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

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Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

 

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

 

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

 

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

 

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

 

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

 

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

 

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

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Adding antihypertensive to standard diabetes therapy improves glycemic control in T2DM

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Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

 

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

 

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

 

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

 

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

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Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

 

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

 

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

 

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

 

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

 

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

 

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

 

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

 

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

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Metformin ups gastrointestinal adverse event risk in T2D

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Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

 

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient 0.89; P = .76) and diarrhea (coefficient 0.344; P = .0437) were higher with metformin IR vs XR.

 

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

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Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

 

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient 0.89; P = .76) and diarrhea (coefficient 0.344; P = .0437) were higher with metformin IR vs XR.

 

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

 

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

 

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient 0.89; P = .76) and diarrhea (coefficient 0.344; P = .0437) were higher with metformin IR vs XR.

 

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

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Metformin may offer more neuroprotection for dementia than sulfonylurea in T2D

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Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

 

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

 

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

 

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

 

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

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Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

 

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

 

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

 

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

 

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

 

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

 

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

 

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

 

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

 

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

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Saxagliptin add-on to oral antihyperglycemic agents safe and effective in drug-naive T2D patients

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Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

 

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were 2.9% (95% CI 3.1% to 2.8%), 2.6% (95% CI 2.8% to 2.5%), and 2.8% (95% CI 2.9% to 2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

 

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

 

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

 

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

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Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

 

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were 2.9% (95% CI 3.1% to 2.8%), 2.6% (95% CI 2.8% to 2.5%), and 2.8% (95% CI 2.9% to 2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

 

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

 

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

 

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

 

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were 2.9% (95% CI 3.1% to 2.8%), 2.6% (95% CI 2.8% to 2.5%), and 2.8% (95% CI 2.9% to 2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

 

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

 

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

 

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

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T2D: Bexagliflozin add-on to metformin shows antidiabetic potency equivalent to glimepiride

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Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

 

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was 0.05% (95% CI 0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

 

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

 

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

 

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

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Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

 

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was 0.05% (95% CI 0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

 

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

 

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

 

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

 

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was 0.05% (95% CI 0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

 

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

 

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

 

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

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T2D: Increased risk for ventricular arrhythmia or sudden cardiac death with sulfonylurea vs metformin

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Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

 

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

 

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

 

Disclosures: This study did not receive any funding. The authors declared no competing interests.

 

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

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Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

 

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

 

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

 

Disclosures: This study did not receive any funding. The authors declared no competing interests.

 

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

 

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

 

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

 

Disclosures: This study did not receive any funding. The authors declared no competing interests.

 

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

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Antidiabetic drugs influence fracture risk in T2D

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Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

 

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

 

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

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Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

 

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

 

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

 

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

 

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

 

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

 

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

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