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10 practice, evidence-based suggestions to improve your gyn practice now
As a new year, and a new decade, open, attention to evidence-based guidelines and to outcomes for individual patients continues to drive medicine. As a busy practicing ObGyn, you’re challenged to sort through the great, and growing, mass of medical information so you can focus on key issues that improve care.
Faced with such a task, it’s not surprising that physicians are notoriously slow to make changes to their practice in response to new evidence.
Here is help. In this article, I present 10 succinct clinical topics and offer medical and surgical suggestions that are easy to put into practice and backed by evidence. If you haven’t already done so, implementing some of these ideas can immediately improve the quality of your care. For each suggestion, I’ve included the pertinent reference.
1. Banish error
Embrace, and immediately implement, surgical time-out and safety checklists for all your surgeries and office procedures.
Altpeter T, Luckhardt K, Lewis JN, Harken AH, Polk HC Jr. Expanded surgical time out: a key to real-time data collection and quality improvement. J Am Coll Surg. 2007;204(4):527–532.
Surgical errors are rare, but we need to continually aim for “zero-error” conditions. These two quality assurance tools may help our efforts.
2. Route of hysterectomy
Make an effort to perform more vaginal hysterectomies and fewer open abdominal hysterectomies.
ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
In cases when vaginal hysterectomy isn’t feasible, consider laparoscopic (or, perhaps, robotic) hysterectomy more often. The role of robotic and single-port hysterectomies continues to evolve.
3. Cystoscopy
Learn, get credentialed for, and perform more diagnostic cystoscopies after certain gynecologic procedures.
ACOG Committee Opinion No. 372, July 2007. The role of cystourethroscopy in the generalist obstetrician-gynecologist practice. Obstet Gynecol. 2007;110(1):221–224.
Cystoscopy is appropriate when a gyn procedure carries at least a 1% risk of lower urinary tract injury. At most centers, that probably includes laparoscopic and robotic hysterectomy and colpopexy.
Simple cystoscopy at hysterectomy,
by Brent E. Seibel, MD
4. Oophorectomy
Perform fewer prophylactic oophorectomies at hysterectomy in low-risk women whose ovaries are normal. When you do remove ovaries as a preventive measure, do so with careful thought and informed consent—especially when the patient is premenopausal.
Parker WH, Broder MS, Chang E, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet Gynecol. 2009;113(5):1027–1037.
In general, we probably perform too many “throw-in” oophorectomies at hysterectomy, with the aim of preventing cancer. But women who keep their ovaries may, in fact, live longer.
Give appropriate and properly timed (within 60 minutes of skin incision) antibiotic prophylaxis for hysterectomy, urogynecology procedures, hysterosalpingography or chromotubation, and surgical abortion.
ACOG Practice Bulletin No. 104: Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009;113(5):1180–1189.
A single-dose antibiotic is adequate before hysterectomy. Give a second dose when surgery will take more than 3 hours or, perhaps, blood loss is expected to be >1,500 mL. Subsequent doses are not indicated for prophylaxis alone. Antibiotic prophylaxis is unnecessary before diagnostic laparoscopy (level-A evidence), hysteroscopic surgery (level-B), or exploratory laparotomy (level-C).
6. Blind biopsy
For evaluation of abnormal uterine bleeding, perform fewer blind endometrial biopsies and more imaging studies, such as transvaginal ultrasonography or saline infusion sonography, or office hysteroscopy.
Goldstein SR. Modern evaluation of the endometrium. Obstet Gynecol. 2010;116(1):168–176.
Blind endometrial biopsy alone yields an unacceptably high rate of false-negative results when utilized to determine the cause of abnormal uterine bleeding.
Pretreat with misoprostol before hysteroscopic procedures.
Choksuchat C. Clinical use of misoprostol in non-pregnant women: review article. J Minim Invasive Gynecol. 2010;17(4):449–455.
Misoprostol eases the force of cervical dilation, results in fewer cervical lacerations and less fluid absorption, and may lead to fewer uterine perforations. The dosage: 200–400 μg orally or intravaginally, at bedtime, for 1 or 2 days before the procedure.
8. Vaginal estrogen
Use intravaginal estrogen therapy as first-line treatment for postmenopausal women who experience vaginal irritation, dyspareunia, and frequent cystitis.
Krause M, Wheeler TL, Richter HE, Snyder TE. Systemic effects of vaginally administered estrogen therapy: a review. Female Pelvic Med Reconstr Surg. 2010;16(3):188–195.
Vaginal estrogen has many clear quality-of-life benefits and carries relatively low risk; risk is probably much lower than what is reported with systemic hormone replacement therapy. Delivery can be by cream, suppository, or vaginal ring. The relatively high cost of vaginal estrogen therapy remains a problem for some women.
9. Vaginal apical support
Consider adding or augmenting some vaginal apical support to help your cystocele repairs.
Summers A, Winkel LA, Hussain HK, DeLancey JOL. The relationship between anterior and apical compartment support. Am J Obstet Gynecol. 2006;194(5):1438– 1443.
In women who have anterior vaginal prolapse (cystocele), approximately half of the prolapse might be explained by a defect in apical attachment. In addition, consider performing prophylactic McCall’s culdoplasty or uterosacral cuff suspension at the time of all hysterectomies, by all routes—even in the absence of prolapse.
Perform fewer, but better-timed, Pap tests.
Sawaya GF. Cervical-cancer screening—new guidelines and the balance between benefits and harms. N Engl J Med. 2009;361(26):2503–2305.
ACOG Practice Bulletin No. 109, December 2009. Cervical cytology screening. Obstet Gynecol. 2009;114(6):1409–1420.
New guidelines for cervical cancer screening that were issued by ACOG in November 2009 are meant to maximize benefit and minimize harm. The guidelines are summarized in the TABLE.
ACOG’s 2009 guidelines for cervical cytology screening
| Age (y) | Recommendation |
|---|---|
| Under 21 | Avoid screening |
| 21–29 | Screen every 2 y |
| 30–65 (or –70) | May screen every 3 y* |
| 65–70 | May discontinue screening† |
| *Applies only to women who have had three consecutive negative cytology tests; exceptions include women who have human immunodeficiency virus infection, compromised immunity, a history of grade-2 or -3 cervical intraepithelial neoplasia, or were exposed in utero to diethylstilbestrol. | |
| †Applies only to women who have had three or more consecutive negative cytology tests and no abnormal tests in the preceding 10 years; exceptions include women who have multiple sexual partners. | |
| Discontinue routine cytology in women who have had a total hysterectomy for benign indications and who do not have a history of high-grade cervical intraepithelial neoplasia (CIN). | |
We want to hear from you! Tell us what you think.
As a new year, and a new decade, open, attention to evidence-based guidelines and to outcomes for individual patients continues to drive medicine. As a busy practicing ObGyn, you’re challenged to sort through the great, and growing, mass of medical information so you can focus on key issues that improve care.
Faced with such a task, it’s not surprising that physicians are notoriously slow to make changes to their practice in response to new evidence.
Here is help. In this article, I present 10 succinct clinical topics and offer medical and surgical suggestions that are easy to put into practice and backed by evidence. If you haven’t already done so, implementing some of these ideas can immediately improve the quality of your care. For each suggestion, I’ve included the pertinent reference.
1. Banish error
Embrace, and immediately implement, surgical time-out and safety checklists for all your surgeries and office procedures.
Altpeter T, Luckhardt K, Lewis JN, Harken AH, Polk HC Jr. Expanded surgical time out: a key to real-time data collection and quality improvement. J Am Coll Surg. 2007;204(4):527–532.
Surgical errors are rare, but we need to continually aim for “zero-error” conditions. These two quality assurance tools may help our efforts.
2. Route of hysterectomy
Make an effort to perform more vaginal hysterectomies and fewer open abdominal hysterectomies.
ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
In cases when vaginal hysterectomy isn’t feasible, consider laparoscopic (or, perhaps, robotic) hysterectomy more often. The role of robotic and single-port hysterectomies continues to evolve.
3. Cystoscopy
Learn, get credentialed for, and perform more diagnostic cystoscopies after certain gynecologic procedures.
ACOG Committee Opinion No. 372, July 2007. The role of cystourethroscopy in the generalist obstetrician-gynecologist practice. Obstet Gynecol. 2007;110(1):221–224.
Cystoscopy is appropriate when a gyn procedure carries at least a 1% risk of lower urinary tract injury. At most centers, that probably includes laparoscopic and robotic hysterectomy and colpopexy.
Simple cystoscopy at hysterectomy,
by Brent E. Seibel, MD
4. Oophorectomy
Perform fewer prophylactic oophorectomies at hysterectomy in low-risk women whose ovaries are normal. When you do remove ovaries as a preventive measure, do so with careful thought and informed consent—especially when the patient is premenopausal.
Parker WH, Broder MS, Chang E, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet Gynecol. 2009;113(5):1027–1037.
In general, we probably perform too many “throw-in” oophorectomies at hysterectomy, with the aim of preventing cancer. But women who keep their ovaries may, in fact, live longer.
Give appropriate and properly timed (within 60 minutes of skin incision) antibiotic prophylaxis for hysterectomy, urogynecology procedures, hysterosalpingography or chromotubation, and surgical abortion.
ACOG Practice Bulletin No. 104: Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009;113(5):1180–1189.
A single-dose antibiotic is adequate before hysterectomy. Give a second dose when surgery will take more than 3 hours or, perhaps, blood loss is expected to be >1,500 mL. Subsequent doses are not indicated for prophylaxis alone. Antibiotic prophylaxis is unnecessary before diagnostic laparoscopy (level-A evidence), hysteroscopic surgery (level-B), or exploratory laparotomy (level-C).
6. Blind biopsy
For evaluation of abnormal uterine bleeding, perform fewer blind endometrial biopsies and more imaging studies, such as transvaginal ultrasonography or saline infusion sonography, or office hysteroscopy.
Goldstein SR. Modern evaluation of the endometrium. Obstet Gynecol. 2010;116(1):168–176.
Blind endometrial biopsy alone yields an unacceptably high rate of false-negative results when utilized to determine the cause of abnormal uterine bleeding.
Pretreat with misoprostol before hysteroscopic procedures.
Choksuchat C. Clinical use of misoprostol in non-pregnant women: review article. J Minim Invasive Gynecol. 2010;17(4):449–455.
Misoprostol eases the force of cervical dilation, results in fewer cervical lacerations and less fluid absorption, and may lead to fewer uterine perforations. The dosage: 200–400 μg orally or intravaginally, at bedtime, for 1 or 2 days before the procedure.
8. Vaginal estrogen
Use intravaginal estrogen therapy as first-line treatment for postmenopausal women who experience vaginal irritation, dyspareunia, and frequent cystitis.
Krause M, Wheeler TL, Richter HE, Snyder TE. Systemic effects of vaginally administered estrogen therapy: a review. Female Pelvic Med Reconstr Surg. 2010;16(3):188–195.
Vaginal estrogen has many clear quality-of-life benefits and carries relatively low risk; risk is probably much lower than what is reported with systemic hormone replacement therapy. Delivery can be by cream, suppository, or vaginal ring. The relatively high cost of vaginal estrogen therapy remains a problem for some women.
9. Vaginal apical support
Consider adding or augmenting some vaginal apical support to help your cystocele repairs.
Summers A, Winkel LA, Hussain HK, DeLancey JOL. The relationship between anterior and apical compartment support. Am J Obstet Gynecol. 2006;194(5):1438– 1443.
In women who have anterior vaginal prolapse (cystocele), approximately half of the prolapse might be explained by a defect in apical attachment. In addition, consider performing prophylactic McCall’s culdoplasty or uterosacral cuff suspension at the time of all hysterectomies, by all routes—even in the absence of prolapse.
Perform fewer, but better-timed, Pap tests.
Sawaya GF. Cervical-cancer screening—new guidelines and the balance between benefits and harms. N Engl J Med. 2009;361(26):2503–2305.
ACOG Practice Bulletin No. 109, December 2009. Cervical cytology screening. Obstet Gynecol. 2009;114(6):1409–1420.
New guidelines for cervical cancer screening that were issued by ACOG in November 2009 are meant to maximize benefit and minimize harm. The guidelines are summarized in the TABLE.
ACOG’s 2009 guidelines for cervical cytology screening
| Age (y) | Recommendation |
|---|---|
| Under 21 | Avoid screening |
| 21–29 | Screen every 2 y |
| 30–65 (or –70) | May screen every 3 y* |
| 65–70 | May discontinue screening† |
| *Applies only to women who have had three consecutive negative cytology tests; exceptions include women who have human immunodeficiency virus infection, compromised immunity, a history of grade-2 or -3 cervical intraepithelial neoplasia, or were exposed in utero to diethylstilbestrol. | |
| †Applies only to women who have had three or more consecutive negative cytology tests and no abnormal tests in the preceding 10 years; exceptions include women who have multiple sexual partners. | |
| Discontinue routine cytology in women who have had a total hysterectomy for benign indications and who do not have a history of high-grade cervical intraepithelial neoplasia (CIN). | |
We want to hear from you! Tell us what you think.
As a new year, and a new decade, open, attention to evidence-based guidelines and to outcomes for individual patients continues to drive medicine. As a busy practicing ObGyn, you’re challenged to sort through the great, and growing, mass of medical information so you can focus on key issues that improve care.
Faced with such a task, it’s not surprising that physicians are notoriously slow to make changes to their practice in response to new evidence.
Here is help. In this article, I present 10 succinct clinical topics and offer medical and surgical suggestions that are easy to put into practice and backed by evidence. If you haven’t already done so, implementing some of these ideas can immediately improve the quality of your care. For each suggestion, I’ve included the pertinent reference.
1. Banish error
Embrace, and immediately implement, surgical time-out and safety checklists for all your surgeries and office procedures.
Altpeter T, Luckhardt K, Lewis JN, Harken AH, Polk HC Jr. Expanded surgical time out: a key to real-time data collection and quality improvement. J Am Coll Surg. 2007;204(4):527–532.
Surgical errors are rare, but we need to continually aim for “zero-error” conditions. These two quality assurance tools may help our efforts.
2. Route of hysterectomy
Make an effort to perform more vaginal hysterectomies and fewer open abdominal hysterectomies.
ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
In cases when vaginal hysterectomy isn’t feasible, consider laparoscopic (or, perhaps, robotic) hysterectomy more often. The role of robotic and single-port hysterectomies continues to evolve.
3. Cystoscopy
Learn, get credentialed for, and perform more diagnostic cystoscopies after certain gynecologic procedures.
ACOG Committee Opinion No. 372, July 2007. The role of cystourethroscopy in the generalist obstetrician-gynecologist practice. Obstet Gynecol. 2007;110(1):221–224.
Cystoscopy is appropriate when a gyn procedure carries at least a 1% risk of lower urinary tract injury. At most centers, that probably includes laparoscopic and robotic hysterectomy and colpopexy.
Simple cystoscopy at hysterectomy,
by Brent E. Seibel, MD
4. Oophorectomy
Perform fewer prophylactic oophorectomies at hysterectomy in low-risk women whose ovaries are normal. When you do remove ovaries as a preventive measure, do so with careful thought and informed consent—especially when the patient is premenopausal.
Parker WH, Broder MS, Chang E, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet Gynecol. 2009;113(5):1027–1037.
In general, we probably perform too many “throw-in” oophorectomies at hysterectomy, with the aim of preventing cancer. But women who keep their ovaries may, in fact, live longer.
Give appropriate and properly timed (within 60 minutes of skin incision) antibiotic prophylaxis for hysterectomy, urogynecology procedures, hysterosalpingography or chromotubation, and surgical abortion.
ACOG Practice Bulletin No. 104: Antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009;113(5):1180–1189.
A single-dose antibiotic is adequate before hysterectomy. Give a second dose when surgery will take more than 3 hours or, perhaps, blood loss is expected to be >1,500 mL. Subsequent doses are not indicated for prophylaxis alone. Antibiotic prophylaxis is unnecessary before diagnostic laparoscopy (level-A evidence), hysteroscopic surgery (level-B), or exploratory laparotomy (level-C).
6. Blind biopsy
For evaluation of abnormal uterine bleeding, perform fewer blind endometrial biopsies and more imaging studies, such as transvaginal ultrasonography or saline infusion sonography, or office hysteroscopy.
Goldstein SR. Modern evaluation of the endometrium. Obstet Gynecol. 2010;116(1):168–176.
Blind endometrial biopsy alone yields an unacceptably high rate of false-negative results when utilized to determine the cause of abnormal uterine bleeding.
Pretreat with misoprostol before hysteroscopic procedures.
Choksuchat C. Clinical use of misoprostol in non-pregnant women: review article. J Minim Invasive Gynecol. 2010;17(4):449–455.
Misoprostol eases the force of cervical dilation, results in fewer cervical lacerations and less fluid absorption, and may lead to fewer uterine perforations. The dosage: 200–400 μg orally or intravaginally, at bedtime, for 1 or 2 days before the procedure.
8. Vaginal estrogen
Use intravaginal estrogen therapy as first-line treatment for postmenopausal women who experience vaginal irritation, dyspareunia, and frequent cystitis.
Krause M, Wheeler TL, Richter HE, Snyder TE. Systemic effects of vaginally administered estrogen therapy: a review. Female Pelvic Med Reconstr Surg. 2010;16(3):188–195.
Vaginal estrogen has many clear quality-of-life benefits and carries relatively low risk; risk is probably much lower than what is reported with systemic hormone replacement therapy. Delivery can be by cream, suppository, or vaginal ring. The relatively high cost of vaginal estrogen therapy remains a problem for some women.
9. Vaginal apical support
Consider adding or augmenting some vaginal apical support to help your cystocele repairs.
Summers A, Winkel LA, Hussain HK, DeLancey JOL. The relationship between anterior and apical compartment support. Am J Obstet Gynecol. 2006;194(5):1438– 1443.
In women who have anterior vaginal prolapse (cystocele), approximately half of the prolapse might be explained by a defect in apical attachment. In addition, consider performing prophylactic McCall’s culdoplasty or uterosacral cuff suspension at the time of all hysterectomies, by all routes—even in the absence of prolapse.
Perform fewer, but better-timed, Pap tests.
Sawaya GF. Cervical-cancer screening—new guidelines and the balance between benefits and harms. N Engl J Med. 2009;361(26):2503–2305.
ACOG Practice Bulletin No. 109, December 2009. Cervical cytology screening. Obstet Gynecol. 2009;114(6):1409–1420.
New guidelines for cervical cancer screening that were issued by ACOG in November 2009 are meant to maximize benefit and minimize harm. The guidelines are summarized in the TABLE.
ACOG’s 2009 guidelines for cervical cytology screening
| Age (y) | Recommendation |
|---|---|
| Under 21 | Avoid screening |
| 21–29 | Screen every 2 y |
| 30–65 (or –70) | May screen every 3 y* |
| 65–70 | May discontinue screening† |
| *Applies only to women who have had three consecutive negative cytology tests; exceptions include women who have human immunodeficiency virus infection, compromised immunity, a history of grade-2 or -3 cervical intraepithelial neoplasia, or were exposed in utero to diethylstilbestrol. | |
| †Applies only to women who have had three or more consecutive negative cytology tests and no abnormal tests in the preceding 10 years; exceptions include women who have multiple sexual partners. | |
| Discontinue routine cytology in women who have had a total hysterectomy for benign indications and who do not have a history of high-grade cervical intraepithelial neoplasia (CIN). | |
We want to hear from you! Tell us what you think.
Management of Psoriasis and Nail DiseaseHighlights of Clinical Symposia
Highlights of Clinical Symposia
A supplement to Skin & Allergy News International
The articles in this supplement are based on presentations made at satellite symposia held July 3, 2010, in Paris, France, and July 3, 2010, in Athens, Greece.
•Contents
•Faculty/Faculty Disclosure
To view the supplement, click the image above.
Contents
Long-Term Benefit-Risk: Interpreting the Evidence
- Psoriasis as a Systemic Disease: Benefit-Risk Considerations
- Long-Term Efficacy: What Do We Really Know?
- Six Years of Infusion Therapy: What Have We Learned?
New Views on Nail Psoriasis and Treatment
- The Magnitude and Impact of Nail Psoriasis
- Understanding the Link Between Psoriasis and Arthritis
- Current Management of Psoriasis With Nail Involvement
Alan Menter, MD
Chief, Division of Dermatology
Baylor University Medical Center
Chair, Psoriasis Research Unit, Baylor Research Institute
Clinical Professor, University of Texas
Southwestern Medical School
Dallas, Texas, USA
Dr Menter is on the advisory board for Abbott Laboratories, Amgen Inc., Astellas Pharma Inc., Centocor Ortho-Biotech Inc., Galderma S.A., Genentech Inc., Warner Chilcott, and Wyeth (Pfizer); is a consultant for Abbott, Amgen, Astellas, Centocor, Eli Lilly and Company, Galderma, Genentech, Stiefel Laboratories, Inc., Warner Chilcott, and Wyeth; is an investigator for Abbott, Allergan Inc., Amgen, Astellas, Asubio Pharma Co., Ltd., Celgene Corporation, Centocor, DUSA Pharmaceuticals, Inc., Eli Lilly, Genentech, Novartis AG, Novo Nordisk Inc., Pfizer, Promius Pharma, LLC, Stiefel, Syntrix Biosystems, Warner Chilcott, and Wyeth; is a speaker for Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Warner Chilcott, and Wyeth; has received grant funds from Abbott, Allergan, Amgen, Astellas, Asubio, Celgene, Centocor, DUSA, Eli Lilly, Genentech, Novartis, Novo Nordisk, Pfizer, Promius, Stiefel, and Syntrix Biosystems; and has received honoraria from Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Stiefel, Warner Chilcott, and Wyeth.
Kristian Reich, MD
Professor of Dermatology
Georg-August-University Gottingen
Partner, Dermatologikum Hamburg
Hamburg, Germany
Dr Reich has received clinical grants from and is a consultant for Abbott, Biogen-Idec, Centocor, Essex, Pfizer, Schering, and Wyeth (Pfizer).
Sergio Chimenti, MD
Chairman and Professor
Department of Dermatology
University of Rome Tor Vergata
Policlinico Tor Vergata
Rome, Italy
Dr Chimenti is a speaker for Schering-Plough Corporation
Robert Baran, MD
Honorary Professor of the University of Franche-Comté
Nail Disease Centre
Cannes, France
Dr Baran has nothing to disclose.
Denis McGonagle, PhD, MB, FRCPI
Professor of Investigative Rheumatology
Academic Unit of Musculoskeletal Disease
University of Leeds
Leeds, United Kingdom
Dr McGonagle has nothing to disclose.
Dimitris Rigopoulos, MD
Assistant Professor of Dermatology
Department of Dermatology, Andreas Syggros Hospital
Athens, Greece
Dr Rigopoulos has nothing to disclose.
A supplement to Skin & Allergy News International
The articles in this supplement are based on presentations made at satellite symposia held July 3, 2010, in Paris, France, and July 3, 2010, in Athens, Greece.
•Contents
•Faculty/Faculty Disclosure
To view the supplement, click the image above.
Contents
Long-Term Benefit-Risk: Interpreting the Evidence
- Psoriasis as a Systemic Disease: Benefit-Risk Considerations
- Long-Term Efficacy: What Do We Really Know?
- Six Years of Infusion Therapy: What Have We Learned?
New Views on Nail Psoriasis and Treatment
- The Magnitude and Impact of Nail Psoriasis
- Understanding the Link Between Psoriasis and Arthritis
- Current Management of Psoriasis With Nail Involvement
Alan Menter, MD
Chief, Division of Dermatology
Baylor University Medical Center
Chair, Psoriasis Research Unit, Baylor Research Institute
Clinical Professor, University of Texas
Southwestern Medical School
Dallas, Texas, USA
Dr Menter is on the advisory board for Abbott Laboratories, Amgen Inc., Astellas Pharma Inc., Centocor Ortho-Biotech Inc., Galderma S.A., Genentech Inc., Warner Chilcott, and Wyeth (Pfizer); is a consultant for Abbott, Amgen, Astellas, Centocor, Eli Lilly and Company, Galderma, Genentech, Stiefel Laboratories, Inc., Warner Chilcott, and Wyeth; is an investigator for Abbott, Allergan Inc., Amgen, Astellas, Asubio Pharma Co., Ltd., Celgene Corporation, Centocor, DUSA Pharmaceuticals, Inc., Eli Lilly, Genentech, Novartis AG, Novo Nordisk Inc., Pfizer, Promius Pharma, LLC, Stiefel, Syntrix Biosystems, Warner Chilcott, and Wyeth; is a speaker for Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Warner Chilcott, and Wyeth; has received grant funds from Abbott, Allergan, Amgen, Astellas, Asubio, Celgene, Centocor, DUSA, Eli Lilly, Genentech, Novartis, Novo Nordisk, Pfizer, Promius, Stiefel, and Syntrix Biosystems; and has received honoraria from Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Stiefel, Warner Chilcott, and Wyeth.
Kristian Reich, MD
Professor of Dermatology
Georg-August-University Gottingen
Partner, Dermatologikum Hamburg
Hamburg, Germany
Dr Reich has received clinical grants from and is a consultant for Abbott, Biogen-Idec, Centocor, Essex, Pfizer, Schering, and Wyeth (Pfizer).
Sergio Chimenti, MD
Chairman and Professor
Department of Dermatology
University of Rome Tor Vergata
Policlinico Tor Vergata
Rome, Italy
Dr Chimenti is a speaker for Schering-Plough Corporation
Robert Baran, MD
Honorary Professor of the University of Franche-Comté
Nail Disease Centre
Cannes, France
Dr Baran has nothing to disclose.
Denis McGonagle, PhD, MB, FRCPI
Professor of Investigative Rheumatology
Academic Unit of Musculoskeletal Disease
University of Leeds
Leeds, United Kingdom
Dr McGonagle has nothing to disclose.
Dimitris Rigopoulos, MD
Assistant Professor of Dermatology
Department of Dermatology, Andreas Syggros Hospital
Athens, Greece
Dr Rigopoulos has nothing to disclose.
A supplement to Skin & Allergy News International
The articles in this supplement are based on presentations made at satellite symposia held July 3, 2010, in Paris, France, and July 3, 2010, in Athens, Greece.
•Contents
•Faculty/Faculty Disclosure
To view the supplement, click the image above.
Contents
Long-Term Benefit-Risk: Interpreting the Evidence
- Psoriasis as a Systemic Disease: Benefit-Risk Considerations
- Long-Term Efficacy: What Do We Really Know?
- Six Years of Infusion Therapy: What Have We Learned?
New Views on Nail Psoriasis and Treatment
- The Magnitude and Impact of Nail Psoriasis
- Understanding the Link Between Psoriasis and Arthritis
- Current Management of Psoriasis With Nail Involvement
Alan Menter, MD
Chief, Division of Dermatology
Baylor University Medical Center
Chair, Psoriasis Research Unit, Baylor Research Institute
Clinical Professor, University of Texas
Southwestern Medical School
Dallas, Texas, USA
Dr Menter is on the advisory board for Abbott Laboratories, Amgen Inc., Astellas Pharma Inc., Centocor Ortho-Biotech Inc., Galderma S.A., Genentech Inc., Warner Chilcott, and Wyeth (Pfizer); is a consultant for Abbott, Amgen, Astellas, Centocor, Eli Lilly and Company, Galderma, Genentech, Stiefel Laboratories, Inc., Warner Chilcott, and Wyeth; is an investigator for Abbott, Allergan Inc., Amgen, Astellas, Asubio Pharma Co., Ltd., Celgene Corporation, Centocor, DUSA Pharmaceuticals, Inc., Eli Lilly, Genentech, Novartis AG, Novo Nordisk Inc., Pfizer, Promius Pharma, LLC, Stiefel, Syntrix Biosystems, Warner Chilcott, and Wyeth; is a speaker for Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Warner Chilcott, and Wyeth; has received grant funds from Abbott, Allergan, Amgen, Astellas, Asubio, Celgene, Centocor, DUSA, Eli Lilly, Genentech, Novartis, Novo Nordisk, Pfizer, Promius, Stiefel, and Syntrix Biosystems; and has received honoraria from Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, Stiefel, Warner Chilcott, and Wyeth.
Kristian Reich, MD
Professor of Dermatology
Georg-August-University Gottingen
Partner, Dermatologikum Hamburg
Hamburg, Germany
Dr Reich has received clinical grants from and is a consultant for Abbott, Biogen-Idec, Centocor, Essex, Pfizer, Schering, and Wyeth (Pfizer).
Sergio Chimenti, MD
Chairman and Professor
Department of Dermatology
University of Rome Tor Vergata
Policlinico Tor Vergata
Rome, Italy
Dr Chimenti is a speaker for Schering-Plough Corporation
Robert Baran, MD
Honorary Professor of the University of Franche-Comté
Nail Disease Centre
Cannes, France
Dr Baran has nothing to disclose.
Denis McGonagle, PhD, MB, FRCPI
Professor of Investigative Rheumatology
Academic Unit of Musculoskeletal Disease
University of Leeds
Leeds, United Kingdom
Dr McGonagle has nothing to disclose.
Dimitris Rigopoulos, MD
Assistant Professor of Dermatology
Department of Dermatology, Andreas Syggros Hospital
Athens, Greece
Dr Rigopoulos has nothing to disclose.
Highlights of Clinical Symposia
Highlights of Clinical Symposia
Photoaging: Fast Facts on Healthier Skin
BEST PRACTICES IN: Managing Eczema With Natural Ingredients
A supplement to Skin & Allergy News. This supplement was sponsored by Johnson & Johnson Consumer Products Company.
- What Role Should Colloidal Oatmeal Play?
- What Other Naturally Derived Ingredients May Benefit Patients With AD?
- The Value of 510(k) Products in Eczema
Faculty/Faculty Disclosure
Lawrence Eichenfield, MD
Chief of Pediatric and Adolescent Dermatology
Rady Children's Hospital and The University of California, San Diego School of Medicine
Professor of Clinical
Pediatrics and Medicine
(Dermatology)
The University of California
San Diego, CA
Dr. Eichenfield was a consultant to Johnson and Johnson.
Melissa Reyes Merin, MD
Clinical Fellow
Rady Children’s Hospital
San Diego, CA
Dr. Reyes Merin has nothing to disclose.
Copyright (c) 2010 Elsevier Inc.
A supplement to Skin & Allergy News. This supplement was sponsored by Johnson & Johnson Consumer Products Company.
- What Role Should Colloidal Oatmeal Play?
- What Other Naturally Derived Ingredients May Benefit Patients With AD?
- The Value of 510(k) Products in Eczema
Faculty/Faculty Disclosure
Lawrence Eichenfield, MD
Chief of Pediatric and Adolescent Dermatology
Rady Children's Hospital and The University of California, San Diego School of Medicine
Professor of Clinical
Pediatrics and Medicine
(Dermatology)
The University of California
San Diego, CA
Dr. Eichenfield was a consultant to Johnson and Johnson.
Melissa Reyes Merin, MD
Clinical Fellow
Rady Children’s Hospital
San Diego, CA
Dr. Reyes Merin has nothing to disclose.
Copyright (c) 2010 Elsevier Inc.
A supplement to Skin & Allergy News. This supplement was sponsored by Johnson & Johnson Consumer Products Company.
- What Role Should Colloidal Oatmeal Play?
- What Other Naturally Derived Ingredients May Benefit Patients With AD?
- The Value of 510(k) Products in Eczema
Faculty/Faculty Disclosure
Lawrence Eichenfield, MD
Chief of Pediatric and Adolescent Dermatology
Rady Children's Hospital and The University of California, San Diego School of Medicine
Professor of Clinical
Pediatrics and Medicine
(Dermatology)
The University of California
San Diego, CA
Dr. Eichenfield was a consultant to Johnson and Johnson.
Melissa Reyes Merin, MD
Clinical Fellow
Rady Children’s Hospital
San Diego, CA
Dr. Reyes Merin has nothing to disclose.
Copyright (c) 2010 Elsevier Inc.
The Role of Human Papillomavirus in Common Skin Conditions: Current Viewpoints and Therapeutic Options
The ORCA (Oracea® for Rosacea: A Community-Based Assessment) Trial: A Large-Scale, Phase 4 Trial in Papulopustular Rosacea
Pelvic repair: Update on correct coding
CPT is a registered trademark® of the American Medical Association.
CPT is a registered trademark® of the American Medical Association.
CPT is a registered trademark® of the American Medical Association.
Introduction
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- The “treat to target” approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control
- Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors
- The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
The number of pharmacologic options available to treat type 2 diabetes mellitus (T2DM) has grown considerably over the past decade. With these options, health care providers have new opportunities to individualize treatment and provide better control of patients’ blood glucose levels. The “treat to failure” approach has been replaced by a “treat to target” approach, with the purpose of quickly achieving the A1C goal of <7.0% in most people, and then intensifying or changing therapy as needed to maintain glycemic control. At the same time, numerous questions have arisen, including where these new treatment options fit along the disease continuum, long-term safety, and how to treat T2DM from the time of diagnosis.
To better understand the questions and clinical challenges faced by primary care physicians, the Primary Care Education Consortium developed and distributed an online survey in February 2010 to primary care clinicians. The survey focused on the incretin class of glucose-lowering agents and was based on the results of reader surveys from 2 previous supplements of The Journal of Family Practice on incretin-based therapies, published in 2008 and 2009. The online survey was completed by 112 of the 1653 individuals (7% response) who received it.
The results of the online survey demonstrated a general understanding of the actions of incretin-based therapies—GLP-1 agonists and DPP-4 inhibitors—but uncertainty regarding their differences and roles in clinical management of patients with T2DM. These uncertainties are a concern because of the progressive nature of T2DM and the increasing importance of these agents in managing patients with T2DM, as reflected in guidelines and consensus statements issued in 2009 by the American Diabetes Association (ADA)/European Association for the Study of Diabetes1 and the American Association of Clinical Endocrinologists/American College of Endocrinology.2
The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options, and from increasing experience not only from well-conducted clinical trials but also in clinical practice. Four incretin-based therapies are now available for use in the United States—exenatide and liraglutide, which are GLP-1 agonists, and sitagliptin and saxagliptin, which are DPP-4 inhibitors; liraglutide and saxagliptin were approved since publication of both guidelines in 2009. Although all are classified as incretin-based therapies, there are distinct differences between the GLP-1 agonists and DPP-4 inhibitors with respect to A1C reduction, effect on weight, and other nonglycemic parameters.
There are many issues with regard to providing comprehensive care to patients with T2DM that could be covered in this supplement. For example, as described in the ADA standards of care,3 the risks of other diseases, such as dyslipidemia, hypertension, and coronary heart disease, must also be considered in management of these patients. Glucose control remains a principal concern, however, and is the primary focus of this supplement.
Driven by results of the February 2010 online survey, this supplement builds upon the 2 previous supplements on incretin-based therapies to address 4 key areas:
- The pathophysiology of T2DM and the unique role of incretin hormones
- Glycemic control differences among available incretin-based agents
- Nonglycemic differences among available incretin-based agents
- Patient education regarding incretin-based therapies to promote patient self-management, with examples of patient cases for which incretin-based therapy is an option
The discussion will take a practical, problem-oriented approach by following 3 cases:
Case 1
A 53-year-old man was diagnosed with T2DM 6 weeks ago, at which time lifestyle intervention was recommended and treatment with metformin 500 mg twice daily was initiated. The patient began to experience severe diarrhea within a few days of beginning metformin. The diarrhea improved over the next 2 to 3 weeks, but he still experiences 1 or 2 episodes every few days. As a result, he does not want to continue taking metformin.
At diagnosis, the patient’s A1C level was 7.5% and his fasting plasma glucose was 158 mg/dL. He is 6-ft 2-in tall, 236 lb, with a body mass index of 30 kg/m2 and blood pressure of 123/78 mm Hg. The patient works full-time as a building contractor, and he is a current smoker. He has hypertriglyceridemia (266 mg/dL), which is being treated with a fibrate.
Case 2
A 47-year-old man was diagnosed with T2DM 2.5 years ago. His A1C level was 8.8%. He had a good response with lifestyle intervention and metformin 1000 mg twice daily, losing 17 lb over 1.5 years. During that time, his A1C level dropped to 7.2%. Six months ago, treatment with pioglitazone 15 mg was started because his A1C level had risen to 7.8%. His current A1C is 7.0%. He is upset because he has since gained 6 lb, mostly edema, which has raised his blood pressure to 138/87 mm Hg. He refuses to take a diuretic, because hydrochlorothiazide, which was prescribed for essential hypertension, caused him to urinate more often. He wants to discontinue pioglitazone so he will lose weight and regain control of his blood pressure.
The patient is 5-ft 9-in tall, 237 lb, with a body mass index of 35 kg/m2. He works full-time as an office manager. He has essential hypertension, which is being treated with lisinopril and metoprolol.
Case 3
A 68-year-old woman was diagnosed with T2DM 5 years ago. Her A1C value was 8.7%. She was initially managed with lifestyle intervention, but 1 year after diagnosis, treatment with metformin 500 mg twice daily was initiated, and the dose was titrated to 1000 mg twice daily a year later. On this regimen, her A1C level dropped to 7.1%, but 1.5 years later, it had increased to 8.3%. At that time, glyburide 5 mg once daily was added to her treatment regimen and titrated to 10 mg once daily. Mild renal insufficiency (CrClest, 58 mL/min) was identified at today’s visit. Her current A1C is 7.4%.
The patient is 5-ft 3-in tall, 148 lb, with a body mass index of 26 kg/m2 and blood pressure of 122/76 mm Hg. She works part-time as a librarian. She has peripheral arterial disease, which is being treated with aspirin, clopidogrel, and atorvastatin. She also has osteoporosis, which is being treated with ibandronate.
These cases, which represent various stages of disease progression, present important decision points regarding how to initiate or modify therapy. For each of these decision points, many factors must be considered, including underlying pathophysiology, comorbidities, A1C-lowering ability, and previous treatment. Other factors to consider are the safety of available agents, including the risk of hypoglycemia; tolerability; and nonglycemic effects, such as on weight, lipids, and blood pressure.
1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.
2. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15:540-559.
3. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(suppl 1):S11-S61.
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- The “treat to target” approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control
- Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors
- The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
The number of pharmacologic options available to treat type 2 diabetes mellitus (T2DM) has grown considerably over the past decade. With these options, health care providers have new opportunities to individualize treatment and provide better control of patients’ blood glucose levels. The “treat to failure” approach has been replaced by a “treat to target” approach, with the purpose of quickly achieving the A1C goal of <7.0% in most people, and then intensifying or changing therapy as needed to maintain glycemic control. At the same time, numerous questions have arisen, including where these new treatment options fit along the disease continuum, long-term safety, and how to treat T2DM from the time of diagnosis.
To better understand the questions and clinical challenges faced by primary care physicians, the Primary Care Education Consortium developed and distributed an online survey in February 2010 to primary care clinicians. The survey focused on the incretin class of glucose-lowering agents and was based on the results of reader surveys from 2 previous supplements of The Journal of Family Practice on incretin-based therapies, published in 2008 and 2009. The online survey was completed by 112 of the 1653 individuals (7% response) who received it.
The results of the online survey demonstrated a general understanding of the actions of incretin-based therapies—GLP-1 agonists and DPP-4 inhibitors—but uncertainty regarding their differences and roles in clinical management of patients with T2DM. These uncertainties are a concern because of the progressive nature of T2DM and the increasing importance of these agents in managing patients with T2DM, as reflected in guidelines and consensus statements issued in 2009 by the American Diabetes Association (ADA)/European Association for the Study of Diabetes1 and the American Association of Clinical Endocrinologists/American College of Endocrinology.2
The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options, and from increasing experience not only from well-conducted clinical trials but also in clinical practice. Four incretin-based therapies are now available for use in the United States—exenatide and liraglutide, which are GLP-1 agonists, and sitagliptin and saxagliptin, which are DPP-4 inhibitors; liraglutide and saxagliptin were approved since publication of both guidelines in 2009. Although all are classified as incretin-based therapies, there are distinct differences between the GLP-1 agonists and DPP-4 inhibitors with respect to A1C reduction, effect on weight, and other nonglycemic parameters.
There are many issues with regard to providing comprehensive care to patients with T2DM that could be covered in this supplement. For example, as described in the ADA standards of care,3 the risks of other diseases, such as dyslipidemia, hypertension, and coronary heart disease, must also be considered in management of these patients. Glucose control remains a principal concern, however, and is the primary focus of this supplement.
Driven by results of the February 2010 online survey, this supplement builds upon the 2 previous supplements on incretin-based therapies to address 4 key areas:
- The pathophysiology of T2DM and the unique role of incretin hormones
- Glycemic control differences among available incretin-based agents
- Nonglycemic differences among available incretin-based agents
- Patient education regarding incretin-based therapies to promote patient self-management, with examples of patient cases for which incretin-based therapy is an option
The discussion will take a practical, problem-oriented approach by following 3 cases:
Case 1
A 53-year-old man was diagnosed with T2DM 6 weeks ago, at which time lifestyle intervention was recommended and treatment with metformin 500 mg twice daily was initiated. The patient began to experience severe diarrhea within a few days of beginning metformin. The diarrhea improved over the next 2 to 3 weeks, but he still experiences 1 or 2 episodes every few days. As a result, he does not want to continue taking metformin.
At diagnosis, the patient’s A1C level was 7.5% and his fasting plasma glucose was 158 mg/dL. He is 6-ft 2-in tall, 236 lb, with a body mass index of 30 kg/m2 and blood pressure of 123/78 mm Hg. The patient works full-time as a building contractor, and he is a current smoker. He has hypertriglyceridemia (266 mg/dL), which is being treated with a fibrate.
Case 2
A 47-year-old man was diagnosed with T2DM 2.5 years ago. His A1C level was 8.8%. He had a good response with lifestyle intervention and metformin 1000 mg twice daily, losing 17 lb over 1.5 years. During that time, his A1C level dropped to 7.2%. Six months ago, treatment with pioglitazone 15 mg was started because his A1C level had risen to 7.8%. His current A1C is 7.0%. He is upset because he has since gained 6 lb, mostly edema, which has raised his blood pressure to 138/87 mm Hg. He refuses to take a diuretic, because hydrochlorothiazide, which was prescribed for essential hypertension, caused him to urinate more often. He wants to discontinue pioglitazone so he will lose weight and regain control of his blood pressure.
The patient is 5-ft 9-in tall, 237 lb, with a body mass index of 35 kg/m2. He works full-time as an office manager. He has essential hypertension, which is being treated with lisinopril and metoprolol.
Case 3
A 68-year-old woman was diagnosed with T2DM 5 years ago. Her A1C value was 8.7%. She was initially managed with lifestyle intervention, but 1 year after diagnosis, treatment with metformin 500 mg twice daily was initiated, and the dose was titrated to 1000 mg twice daily a year later. On this regimen, her A1C level dropped to 7.1%, but 1.5 years later, it had increased to 8.3%. At that time, glyburide 5 mg once daily was added to her treatment regimen and titrated to 10 mg once daily. Mild renal insufficiency (CrClest, 58 mL/min) was identified at today’s visit. Her current A1C is 7.4%.
The patient is 5-ft 3-in tall, 148 lb, with a body mass index of 26 kg/m2 and blood pressure of 122/76 mm Hg. She works part-time as a librarian. She has peripheral arterial disease, which is being treated with aspirin, clopidogrel, and atorvastatin. She also has osteoporosis, which is being treated with ibandronate.
These cases, which represent various stages of disease progression, present important decision points regarding how to initiate or modify therapy. For each of these decision points, many factors must be considered, including underlying pathophysiology, comorbidities, A1C-lowering ability, and previous treatment. Other factors to consider are the safety of available agents, including the risk of hypoglycemia; tolerability; and nonglycemic effects, such as on weight, lipids, and blood pressure.
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- The “treat to target” approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control
- Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors
- The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
The number of pharmacologic options available to treat type 2 diabetes mellitus (T2DM) has grown considerably over the past decade. With these options, health care providers have new opportunities to individualize treatment and provide better control of patients’ blood glucose levels. The “treat to failure” approach has been replaced by a “treat to target” approach, with the purpose of quickly achieving the A1C goal of <7.0% in most people, and then intensifying or changing therapy as needed to maintain glycemic control. At the same time, numerous questions have arisen, including where these new treatment options fit along the disease continuum, long-term safety, and how to treat T2DM from the time of diagnosis.
To better understand the questions and clinical challenges faced by primary care physicians, the Primary Care Education Consortium developed and distributed an online survey in February 2010 to primary care clinicians. The survey focused on the incretin class of glucose-lowering agents and was based on the results of reader surveys from 2 previous supplements of The Journal of Family Practice on incretin-based therapies, published in 2008 and 2009. The online survey was completed by 112 of the 1653 individuals (7% response) who received it.
The results of the online survey demonstrated a general understanding of the actions of incretin-based therapies—GLP-1 agonists and DPP-4 inhibitors—but uncertainty regarding their differences and roles in clinical management of patients with T2DM. These uncertainties are a concern because of the progressive nature of T2DM and the increasing importance of these agents in managing patients with T2DM, as reflected in guidelines and consensus statements issued in 2009 by the American Diabetes Association (ADA)/European Association for the Study of Diabetes1 and the American Association of Clinical Endocrinologists/American College of Endocrinology.2
The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options, and from increasing experience not only from well-conducted clinical trials but also in clinical practice. Four incretin-based therapies are now available for use in the United States—exenatide and liraglutide, which are GLP-1 agonists, and sitagliptin and saxagliptin, which are DPP-4 inhibitors; liraglutide and saxagliptin were approved since publication of both guidelines in 2009. Although all are classified as incretin-based therapies, there are distinct differences between the GLP-1 agonists and DPP-4 inhibitors with respect to A1C reduction, effect on weight, and other nonglycemic parameters.
There are many issues with regard to providing comprehensive care to patients with T2DM that could be covered in this supplement. For example, as described in the ADA standards of care,3 the risks of other diseases, such as dyslipidemia, hypertension, and coronary heart disease, must also be considered in management of these patients. Glucose control remains a principal concern, however, and is the primary focus of this supplement.
Driven by results of the February 2010 online survey, this supplement builds upon the 2 previous supplements on incretin-based therapies to address 4 key areas:
- The pathophysiology of T2DM and the unique role of incretin hormones
- Glycemic control differences among available incretin-based agents
- Nonglycemic differences among available incretin-based agents
- Patient education regarding incretin-based therapies to promote patient self-management, with examples of patient cases for which incretin-based therapy is an option
The discussion will take a practical, problem-oriented approach by following 3 cases:
Case 1
A 53-year-old man was diagnosed with T2DM 6 weeks ago, at which time lifestyle intervention was recommended and treatment with metformin 500 mg twice daily was initiated. The patient began to experience severe diarrhea within a few days of beginning metformin. The diarrhea improved over the next 2 to 3 weeks, but he still experiences 1 or 2 episodes every few days. As a result, he does not want to continue taking metformin.
At diagnosis, the patient’s A1C level was 7.5% and his fasting plasma glucose was 158 mg/dL. He is 6-ft 2-in tall, 236 lb, with a body mass index of 30 kg/m2 and blood pressure of 123/78 mm Hg. The patient works full-time as a building contractor, and he is a current smoker. He has hypertriglyceridemia (266 mg/dL), which is being treated with a fibrate.
Case 2
A 47-year-old man was diagnosed with T2DM 2.5 years ago. His A1C level was 8.8%. He had a good response with lifestyle intervention and metformin 1000 mg twice daily, losing 17 lb over 1.5 years. During that time, his A1C level dropped to 7.2%. Six months ago, treatment with pioglitazone 15 mg was started because his A1C level had risen to 7.8%. His current A1C is 7.0%. He is upset because he has since gained 6 lb, mostly edema, which has raised his blood pressure to 138/87 mm Hg. He refuses to take a diuretic, because hydrochlorothiazide, which was prescribed for essential hypertension, caused him to urinate more often. He wants to discontinue pioglitazone so he will lose weight and regain control of his blood pressure.
The patient is 5-ft 9-in tall, 237 lb, with a body mass index of 35 kg/m2. He works full-time as an office manager. He has essential hypertension, which is being treated with lisinopril and metoprolol.
Case 3
A 68-year-old woman was diagnosed with T2DM 5 years ago. Her A1C value was 8.7%. She was initially managed with lifestyle intervention, but 1 year after diagnosis, treatment with metformin 500 mg twice daily was initiated, and the dose was titrated to 1000 mg twice daily a year later. On this regimen, her A1C level dropped to 7.1%, but 1.5 years later, it had increased to 8.3%. At that time, glyburide 5 mg once daily was added to her treatment regimen and titrated to 10 mg once daily. Mild renal insufficiency (CrClest, 58 mL/min) was identified at today’s visit. Her current A1C is 7.4%.
The patient is 5-ft 3-in tall, 148 lb, with a body mass index of 26 kg/m2 and blood pressure of 122/76 mm Hg. She works part-time as a librarian. She has peripheral arterial disease, which is being treated with aspirin, clopidogrel, and atorvastatin. She also has osteoporosis, which is being treated with ibandronate.
These cases, which represent various stages of disease progression, present important decision points regarding how to initiate or modify therapy. For each of these decision points, many factors must be considered, including underlying pathophysiology, comorbidities, A1C-lowering ability, and previous treatment. Other factors to consider are the safety of available agents, including the risk of hypoglycemia; tolerability; and nonglycemic effects, such as on weight, lipids, and blood pressure.
1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.
2. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15:540-559.
3. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(suppl 1):S11-S61.
1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.
2. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15:540-559.
3. Standards of medical care in diabetes—2010. Diabetes Care. 2010;33(suppl 1):S11-S61.
Optimizing Topical Therapies for Treating Psoriasis: A Consensus Conference
Patient education and self-management
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- Patient education, which is essential for successful patient self-management, can be provided by a multidisciplinary diabetes care team
- The dosing and administration of glucagon-like peptide (GLP)-1 agonists or dipeptidyl peptidase (DPP)-4 inhibitors offer significant flexibility to meet patient needs
- The GLP-1 agonists and DPP-4 inhibitors vary in administration, effect on weight, contraindications, and dosing adjustments for patients with renal impairment
- The relatively high cost ($7 to $14 per day) of therapy with a GLP-1 agonist or DPP-4 inhibitor may be covered by insurance, so cost to the patient may be limited to copays
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
Introduction
The comprehensive and long-term management of patients with type 2 diabetes mellitus (T2DM) requires that they assume primary responsibility for daily self-management. For this to occur, patient education is critical, yet it is time-consuming. Because our time as primary care physicians is limited, developing a diabetes care team, even informally, can be helpful in providing the comprehensive care that is needed. Beyond easing the amount of time we need to provide the patient education required, the patient is able to benefit from the specialized skills and knowledge of other team members, such as a nurse, pharmacist, dietitian, certified diabetes educator, or an exercise specialist. It is important, however, that as primary care physicians, we coordinate the care provided by the team so that treatment goals are clear, communication is maintained, and patient outcomes are optimal.
With this need for patient self-management supported by ongoing education in mind, let’s turn our attention to some issues of special importance with respect to the GLP-1 agonists and DPP-4 inhibitors.
Dosing and administration
There is considerable variability among the GLP-1 agonists and DPP-4 inhibitors with respect to their dosing and administration (TABLE).1-4 This variability enables you and your patients to select a treatment that best meets their needs.
Case 2
As you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options for modifying his therapy, this 47-year-old office manager wants to know what side effects are likely and which, if any, might pose a problem at work.
You can begin by telling the patient that transient nausea has been a common occurrence in patients treated with a GLP-1 agonist and that a key factor regarding this side effect is how the medication is titrated (see accompanying article “Safety, tolerability, and nonglycemic effects of incretin-based therapies”). Exenatide and liraglutide should be administered using the dose escalation strategy outlined in the TABLE. You tell him that nausea is typically mild and usually peaks within 8 weeks of commencing treatment with exenatide5 and within 4 to 6 weeks with liraglutide.6,7 Should nausea persist and be troublesome, taking liraglutide with food has been helpful for some patients; otherwise, liraglutide can be taken at the same time each day irrespective of meals.2 You also note that saxagliptin and sitagliptin can be taken with or without food.3,4 While the prescribing information indicates that exenatide can be taken at any time within the 60-minute period before a meal,1 exenatide can be administered during but not after the meal if necessary to reduce nausea, without sacrificing its glucose-lowering effects8; the satiety effect, however, may be blunted in some patients. Reduction in the postprandial glucose level has been shown to be greatest when exenatide is taken between 60 minutes before or by the end of the meal. Exenatide should not be taken after the meal, because transient low blood glucose levels may occur.8
In patients with renal dysfunction, the dose of sitagliptin and saxagliptin but not liraglutide needs to be adjusted (TABLE).1-4 Exenatide should not be used in patients with a CrCl <30 mL/min. Exenatide and sitagliptin are contraindicated in patients with a known hypersensitivity reaction to the drug.1,3 Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia (MEN) syndrome type 2.2 There are no contraindications listed for saxagliptin.4
TABLE
| GLP-1 | DPP-4 | |||
|---|---|---|---|---|
| Exenatide1 | Liraglutide2 | Sitagliptin3 | Saxagliptin4 | |
| Route | Subcutaneous | Subcutaneous | Oral | Oral |
| Frequency | Twice daily | Once daily | Once daily | Once daily |
| Relation to meals | Within 60 min prior to eating | With/without food | With/without food | With/without food |
| Timing | Before the 2 main daily meals, ≥6 h apart | Any time of day | Any time of day | Any time of day |
| Dosing, initial | 5 μg BID; increase to 10 μg BID after 1 mo if needed for glucose control | 0.6 mg OD x 1 week, then 1.2 mg OD; increase to 1.8 mg OD if needed for glucose control | 100 mg OD | 2.5 mg or 5 mg OD |
| Dosing, renal disease | Do not use if CrCl <30 mL/min or in ESRD; use with caution in patient with renal transplantation | No adjustment; use with caution | CrCl ≥30 to <50 mL/min, 50 mg OD; CrCl <30 mL/min or ESRD requiring dialysis, 25 mg OD | CrCl ≤50 mL/min or ESRD requiring hemo-dialysis, 2.5 mg OD |
| BID, twice daily; CrCl, creatinine clearance; ESRD, end-stage renal disease; OD, once daily. | ||||
Case 1
During your discussion with this building contractor, you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options. You begin to discuss the need to self-inject the GLP-1 agonist, when he interrupts you and tells you that he does not want to hear anything about insulin or other medications that would require him to self-inject, because his work environment and schedule would make this impossible.
While his feelings are understandable, open communication with this patient can do much to allay his concerns. Although concerns about injecting outside the home are common with insulin, the need for this with a GLP-1 agonist is unlikely because of the twice-daily exenatide and once-daily liraglutide dosing schedules and the lack of need to intensely monitor blood glucose levels. However, if the patient eats breakfast at work or doesn’t eat breakfast at all, this may become an issue with exenatide because of the need to eat within 60 minutes of taking a dose.
Concerns about self-injecting also can be addressed by showing patients the pen injection device and its small-gauge needle and instructing them in its use. Having a patient self-inject the first dose in the office can relieve much anxiety. Patients often comment about how easy and painless it is to inject themselves. One caution, however, is that if a patient self-injects a dose of exenatide in the office, he or she must be reminded of the need to eat within the next hour.
Talking about risks
Case 3
During your discussion with this 68-year-old woman about modifying her therapy, you include the GLP-1 agonists and DPP-4 inhibitors as treatment options. She replies, “Yes, I’ve seen information about them at my job at the library. They can cause cancer, can’t they?”
This comment highlights the importance of talking openly with patients to help them make good decisions about their health. Discussions often focus on the anticipated benefits of medications, but as we know, there are risks associated with every medication choice. Initially discussing risks with this patient could avoid having her return to the office angry with you for not warning her before she began taking the medication.
In this situation, as part of your discussion about liraglutide, you could refer her to the manufacturer’s Web site for information about the Risk Evaluation and Mitigation Strategy (REMS) program for liraglutide, sitagliptin, and saxagliptin. You also could provide her with the patient medication guide included with the program. REMS programs have been implemented for several glucose-lowering medications, since implementation of the REMS program by the US Food and Drug Administration (FDA) in 2007; these include exenatide, liraglutide, pioglitazone with or without glimepiride, rosiglitazone with or without glimepiride, and sitagliptin with or without metformin. Medication guides and other information are available online from the FDA at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.
Medication cost
Case 3
You continue your discussion with this 68-year-old part-time librarian about the benefits and risks of insulin, a thiazolidinedione, and a glinide, as well as a GLP-1 agonist and a DPP-4 inhibitor. Suddenly she asks you how much these medications cost.
The cost of health care in general and medications in particular continue to dominate discussions. This is especially true for medications that have arrived on the market more recently, including the GLP-1 agonists and the DPP-4 inhibitors, which range in cost from about $7 to $14 per day.9-12 These agents, however, may be covered by health insurance, so cost to the patient may be limited to copays. The lower risk of hypoglycemia observed with the GLP-1 agonists and DPP-4 inhibitors compared with some other glucose-lowering therapies may make it possible to perform self-monitoring of blood glucose less frequently, but this is an individual patient issue.
Although it may be difficult or uncomfortable to talk about the costs of treatment, it has a great impact on medication adherence and overall treatment satisfaction. In this case, in addition to discussing insurance coverage and what she can afford, you should also talk with the patient about ways the cost of her medications might be reduced.
While no generic formulations are available for exenatide, liraglutide, saxagliptin, or sitagliptin, each manufacturer offers a prescription assistance program. Patients should also be encouraged to check manufacturers’ Web sites for available coupons or discount programs.
With this patient, you also might talk about how different medications can affect total cost of her diabetes treatment differently. Limited retrospective analyses suggest that compared with glimepiride, liraglutide reduces the total cost of care, including care for ocular events and neuropathy leading to amputation.13 Other studies indicate that the overall cost of care with exenatide is lower than with insulin glargine,14 including care for hypoglycemia-related events.15
Summary
Working closely with patients and providing ongoing education, ideally in conjunction with a diabetes care team, can help ensure that the best treatment options are selected for an individual patient and that the patient is capable of effective self-management.
1. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2009.
2. Victoza [package insert]. Princeton, NJ: Novo Nordisk Inc; 2010.
3. Januvia [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; February 2, 2010.
4. Onglyza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
5. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092-1100.
6. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473-481.
7. Nauck M, Frid A, Hermansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84-90.
8. Linnebjerg H, Kothare PA, Skrivanek Z, et al. Exenatide: effect of injection time on postprandial glucose in patients with type 2 diabetes. Diabet Med. 2006;23:240-245.
9. Byetta (exenatide) pen. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=66780021201&trx=1Z5005. Accessed August 18, 2010.
10. Januvia (sitagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/drugindex/rxsearch.asp?drug=Januvia&trx=1Z5005. Accessed August 18, 2010.
11. Onglyza (saxagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00003421521&trx=1Z5006. Accessed August 18, 2010.
12. Victoza (liraglutide) injection. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00169406012&trx=1Z5006. Accessed August 18, 2010.
13. Sullivan SD, Alfonso-Cristancho R, Conner C, et al. A simulation of the comparative long-term effectiveness of liraglutide and glimepiride monotherapies in patients with type 2 diabetes mellitus. Pharmacotherapy. 2009;29:1280-1288.
14. Misurski D, Lage MJ, Fabunmi R, et al. A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine. Appl Health Econ Health Policy. 2009;7:245-254.
15. Fabunmi R, Nielsen LL, Quimbo R, et al. Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine. Curr Med Res Opin. 2009;25:777-786.
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- Patient education, which is essential for successful patient self-management, can be provided by a multidisciplinary diabetes care team
- The dosing and administration of glucagon-like peptide (GLP)-1 agonists or dipeptidyl peptidase (DPP)-4 inhibitors offer significant flexibility to meet patient needs
- The GLP-1 agonists and DPP-4 inhibitors vary in administration, effect on weight, contraindications, and dosing adjustments for patients with renal impairment
- The relatively high cost ($7 to $14 per day) of therapy with a GLP-1 agonist or DPP-4 inhibitor may be covered by insurance, so cost to the patient may be limited to copays
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
Introduction
The comprehensive and long-term management of patients with type 2 diabetes mellitus (T2DM) requires that they assume primary responsibility for daily self-management. For this to occur, patient education is critical, yet it is time-consuming. Because our time as primary care physicians is limited, developing a diabetes care team, even informally, can be helpful in providing the comprehensive care that is needed. Beyond easing the amount of time we need to provide the patient education required, the patient is able to benefit from the specialized skills and knowledge of other team members, such as a nurse, pharmacist, dietitian, certified diabetes educator, or an exercise specialist. It is important, however, that as primary care physicians, we coordinate the care provided by the team so that treatment goals are clear, communication is maintained, and patient outcomes are optimal.
With this need for patient self-management supported by ongoing education in mind, let’s turn our attention to some issues of special importance with respect to the GLP-1 agonists and DPP-4 inhibitors.
Dosing and administration
There is considerable variability among the GLP-1 agonists and DPP-4 inhibitors with respect to their dosing and administration (TABLE).1-4 This variability enables you and your patients to select a treatment that best meets their needs.
Case 2
As you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options for modifying his therapy, this 47-year-old office manager wants to know what side effects are likely and which, if any, might pose a problem at work.
You can begin by telling the patient that transient nausea has been a common occurrence in patients treated with a GLP-1 agonist and that a key factor regarding this side effect is how the medication is titrated (see accompanying article “Safety, tolerability, and nonglycemic effects of incretin-based therapies”). Exenatide and liraglutide should be administered using the dose escalation strategy outlined in the TABLE. You tell him that nausea is typically mild and usually peaks within 8 weeks of commencing treatment with exenatide5 and within 4 to 6 weeks with liraglutide.6,7 Should nausea persist and be troublesome, taking liraglutide with food has been helpful for some patients; otherwise, liraglutide can be taken at the same time each day irrespective of meals.2 You also note that saxagliptin and sitagliptin can be taken with or without food.3,4 While the prescribing information indicates that exenatide can be taken at any time within the 60-minute period before a meal,1 exenatide can be administered during but not after the meal if necessary to reduce nausea, without sacrificing its glucose-lowering effects8; the satiety effect, however, may be blunted in some patients. Reduction in the postprandial glucose level has been shown to be greatest when exenatide is taken between 60 minutes before or by the end of the meal. Exenatide should not be taken after the meal, because transient low blood glucose levels may occur.8
In patients with renal dysfunction, the dose of sitagliptin and saxagliptin but not liraglutide needs to be adjusted (TABLE).1-4 Exenatide should not be used in patients with a CrCl <30 mL/min. Exenatide and sitagliptin are contraindicated in patients with a known hypersensitivity reaction to the drug.1,3 Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia (MEN) syndrome type 2.2 There are no contraindications listed for saxagliptin.4
TABLE
| GLP-1 | DPP-4 | |||
|---|---|---|---|---|
| Exenatide1 | Liraglutide2 | Sitagliptin3 | Saxagliptin4 | |
| Route | Subcutaneous | Subcutaneous | Oral | Oral |
| Frequency | Twice daily | Once daily | Once daily | Once daily |
| Relation to meals | Within 60 min prior to eating | With/without food | With/without food | With/without food |
| Timing | Before the 2 main daily meals, ≥6 h apart | Any time of day | Any time of day | Any time of day |
| Dosing, initial | 5 μg BID; increase to 10 μg BID after 1 mo if needed for glucose control | 0.6 mg OD x 1 week, then 1.2 mg OD; increase to 1.8 mg OD if needed for glucose control | 100 mg OD | 2.5 mg or 5 mg OD |
| Dosing, renal disease | Do not use if CrCl <30 mL/min or in ESRD; use with caution in patient with renal transplantation | No adjustment; use with caution | CrCl ≥30 to <50 mL/min, 50 mg OD; CrCl <30 mL/min or ESRD requiring dialysis, 25 mg OD | CrCl ≤50 mL/min or ESRD requiring hemo-dialysis, 2.5 mg OD |
| BID, twice daily; CrCl, creatinine clearance; ESRD, end-stage renal disease; OD, once daily. | ||||
Case 1
During your discussion with this building contractor, you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options. You begin to discuss the need to self-inject the GLP-1 agonist, when he interrupts you and tells you that he does not want to hear anything about insulin or other medications that would require him to self-inject, because his work environment and schedule would make this impossible.
While his feelings are understandable, open communication with this patient can do much to allay his concerns. Although concerns about injecting outside the home are common with insulin, the need for this with a GLP-1 agonist is unlikely because of the twice-daily exenatide and once-daily liraglutide dosing schedules and the lack of need to intensely monitor blood glucose levels. However, if the patient eats breakfast at work or doesn’t eat breakfast at all, this may become an issue with exenatide because of the need to eat within 60 minutes of taking a dose.
Concerns about self-injecting also can be addressed by showing patients the pen injection device and its small-gauge needle and instructing them in its use. Having a patient self-inject the first dose in the office can relieve much anxiety. Patients often comment about how easy and painless it is to inject themselves. One caution, however, is that if a patient self-injects a dose of exenatide in the office, he or she must be reminded of the need to eat within the next hour.
Talking about risks
Case 3
During your discussion with this 68-year-old woman about modifying her therapy, you include the GLP-1 agonists and DPP-4 inhibitors as treatment options. She replies, “Yes, I’ve seen information about them at my job at the library. They can cause cancer, can’t they?”
This comment highlights the importance of talking openly with patients to help them make good decisions about their health. Discussions often focus on the anticipated benefits of medications, but as we know, there are risks associated with every medication choice. Initially discussing risks with this patient could avoid having her return to the office angry with you for not warning her before she began taking the medication.
In this situation, as part of your discussion about liraglutide, you could refer her to the manufacturer’s Web site for information about the Risk Evaluation and Mitigation Strategy (REMS) program for liraglutide, sitagliptin, and saxagliptin. You also could provide her with the patient medication guide included with the program. REMS programs have been implemented for several glucose-lowering medications, since implementation of the REMS program by the US Food and Drug Administration (FDA) in 2007; these include exenatide, liraglutide, pioglitazone with or without glimepiride, rosiglitazone with or without glimepiride, and sitagliptin with or without metformin. Medication guides and other information are available online from the FDA at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.
Medication cost
Case 3
You continue your discussion with this 68-year-old part-time librarian about the benefits and risks of insulin, a thiazolidinedione, and a glinide, as well as a GLP-1 agonist and a DPP-4 inhibitor. Suddenly she asks you how much these medications cost.
The cost of health care in general and medications in particular continue to dominate discussions. This is especially true for medications that have arrived on the market more recently, including the GLP-1 agonists and the DPP-4 inhibitors, which range in cost from about $7 to $14 per day.9-12 These agents, however, may be covered by health insurance, so cost to the patient may be limited to copays. The lower risk of hypoglycemia observed with the GLP-1 agonists and DPP-4 inhibitors compared with some other glucose-lowering therapies may make it possible to perform self-monitoring of blood glucose less frequently, but this is an individual patient issue.
Although it may be difficult or uncomfortable to talk about the costs of treatment, it has a great impact on medication adherence and overall treatment satisfaction. In this case, in addition to discussing insurance coverage and what she can afford, you should also talk with the patient about ways the cost of her medications might be reduced.
While no generic formulations are available for exenatide, liraglutide, saxagliptin, or sitagliptin, each manufacturer offers a prescription assistance program. Patients should also be encouraged to check manufacturers’ Web sites for available coupons or discount programs.
With this patient, you also might talk about how different medications can affect total cost of her diabetes treatment differently. Limited retrospective analyses suggest that compared with glimepiride, liraglutide reduces the total cost of care, including care for ocular events and neuropathy leading to amputation.13 Other studies indicate that the overall cost of care with exenatide is lower than with insulin glargine,14 including care for hypoglycemia-related events.15
Summary
Working closely with patients and providing ongoing education, ideally in conjunction with a diabetes care team, can help ensure that the best treatment options are selected for an individual patient and that the patient is capable of effective self-management.
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
- Patient education, which is essential for successful patient self-management, can be provided by a multidisciplinary diabetes care team
- The dosing and administration of glucagon-like peptide (GLP)-1 agonists or dipeptidyl peptidase (DPP)-4 inhibitors offer significant flexibility to meet patient needs
- The GLP-1 agonists and DPP-4 inhibitors vary in administration, effect on weight, contraindications, and dosing adjustments for patients with renal impairment
- The relatively high cost ($7 to $14 per day) of therapy with a GLP-1 agonist or DPP-4 inhibitor may be covered by insurance, so cost to the patient may be limited to copays
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
Introduction
The comprehensive and long-term management of patients with type 2 diabetes mellitus (T2DM) requires that they assume primary responsibility for daily self-management. For this to occur, patient education is critical, yet it is time-consuming. Because our time as primary care physicians is limited, developing a diabetes care team, even informally, can be helpful in providing the comprehensive care that is needed. Beyond easing the amount of time we need to provide the patient education required, the patient is able to benefit from the specialized skills and knowledge of other team members, such as a nurse, pharmacist, dietitian, certified diabetes educator, or an exercise specialist. It is important, however, that as primary care physicians, we coordinate the care provided by the team so that treatment goals are clear, communication is maintained, and patient outcomes are optimal.
With this need for patient self-management supported by ongoing education in mind, let’s turn our attention to some issues of special importance with respect to the GLP-1 agonists and DPP-4 inhibitors.
Dosing and administration
There is considerable variability among the GLP-1 agonists and DPP-4 inhibitors with respect to their dosing and administration (TABLE).1-4 This variability enables you and your patients to select a treatment that best meets their needs.
Case 2
As you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options for modifying his therapy, this 47-year-old office manager wants to know what side effects are likely and which, if any, might pose a problem at work.
You can begin by telling the patient that transient nausea has been a common occurrence in patients treated with a GLP-1 agonist and that a key factor regarding this side effect is how the medication is titrated (see accompanying article “Safety, tolerability, and nonglycemic effects of incretin-based therapies”). Exenatide and liraglutide should be administered using the dose escalation strategy outlined in the TABLE. You tell him that nausea is typically mild and usually peaks within 8 weeks of commencing treatment with exenatide5 and within 4 to 6 weeks with liraglutide.6,7 Should nausea persist and be troublesome, taking liraglutide with food has been helpful for some patients; otherwise, liraglutide can be taken at the same time each day irrespective of meals.2 You also note that saxagliptin and sitagliptin can be taken with or without food.3,4 While the prescribing information indicates that exenatide can be taken at any time within the 60-minute period before a meal,1 exenatide can be administered during but not after the meal if necessary to reduce nausea, without sacrificing its glucose-lowering effects8; the satiety effect, however, may be blunted in some patients. Reduction in the postprandial glucose level has been shown to be greatest when exenatide is taken between 60 minutes before or by the end of the meal. Exenatide should not be taken after the meal, because transient low blood glucose levels may occur.8
In patients with renal dysfunction, the dose of sitagliptin and saxagliptin but not liraglutide needs to be adjusted (TABLE).1-4 Exenatide should not be used in patients with a CrCl <30 mL/min. Exenatide and sitagliptin are contraindicated in patients with a known hypersensitivity reaction to the drug.1,3 Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia (MEN) syndrome type 2.2 There are no contraindications listed for saxagliptin.4
TABLE
| GLP-1 | DPP-4 | |||
|---|---|---|---|---|
| Exenatide1 | Liraglutide2 | Sitagliptin3 | Saxagliptin4 | |
| Route | Subcutaneous | Subcutaneous | Oral | Oral |
| Frequency | Twice daily | Once daily | Once daily | Once daily |
| Relation to meals | Within 60 min prior to eating | With/without food | With/without food | With/without food |
| Timing | Before the 2 main daily meals, ≥6 h apart | Any time of day | Any time of day | Any time of day |
| Dosing, initial | 5 μg BID; increase to 10 μg BID after 1 mo if needed for glucose control | 0.6 mg OD x 1 week, then 1.2 mg OD; increase to 1.8 mg OD if needed for glucose control | 100 mg OD | 2.5 mg or 5 mg OD |
| Dosing, renal disease | Do not use if CrCl <30 mL/min or in ESRD; use with caution in patient with renal transplantation | No adjustment; use with caution | CrCl ≥30 to <50 mL/min, 50 mg OD; CrCl <30 mL/min or ESRD requiring dialysis, 25 mg OD | CrCl ≤50 mL/min or ESRD requiring hemo-dialysis, 2.5 mg OD |
| BID, twice daily; CrCl, creatinine clearance; ESRD, end-stage renal disease; OD, once daily. | ||||
Case 1
During your discussion with this building contractor, you begin to talk about the GLP-1 agonists and DPP-4 inhibitors as treatment options. You begin to discuss the need to self-inject the GLP-1 agonist, when he interrupts you and tells you that he does not want to hear anything about insulin or other medications that would require him to self-inject, because his work environment and schedule would make this impossible.
While his feelings are understandable, open communication with this patient can do much to allay his concerns. Although concerns about injecting outside the home are common with insulin, the need for this with a GLP-1 agonist is unlikely because of the twice-daily exenatide and once-daily liraglutide dosing schedules and the lack of need to intensely monitor blood glucose levels. However, if the patient eats breakfast at work or doesn’t eat breakfast at all, this may become an issue with exenatide because of the need to eat within 60 minutes of taking a dose.
Concerns about self-injecting also can be addressed by showing patients the pen injection device and its small-gauge needle and instructing them in its use. Having a patient self-inject the first dose in the office can relieve much anxiety. Patients often comment about how easy and painless it is to inject themselves. One caution, however, is that if a patient self-injects a dose of exenatide in the office, he or she must be reminded of the need to eat within the next hour.
Talking about risks
Case 3
During your discussion with this 68-year-old woman about modifying her therapy, you include the GLP-1 agonists and DPP-4 inhibitors as treatment options. She replies, “Yes, I’ve seen information about them at my job at the library. They can cause cancer, can’t they?”
This comment highlights the importance of talking openly with patients to help them make good decisions about their health. Discussions often focus on the anticipated benefits of medications, but as we know, there are risks associated with every medication choice. Initially discussing risks with this patient could avoid having her return to the office angry with you for not warning her before she began taking the medication.
In this situation, as part of your discussion about liraglutide, you could refer her to the manufacturer’s Web site for information about the Risk Evaluation and Mitigation Strategy (REMS) program for liraglutide, sitagliptin, and saxagliptin. You also could provide her with the patient medication guide included with the program. REMS programs have been implemented for several glucose-lowering medications, since implementation of the REMS program by the US Food and Drug Administration (FDA) in 2007; these include exenatide, liraglutide, pioglitazone with or without glimepiride, rosiglitazone with or without glimepiride, and sitagliptin with or without metformin. Medication guides and other information are available online from the FDA at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.
Medication cost
Case 3
You continue your discussion with this 68-year-old part-time librarian about the benefits and risks of insulin, a thiazolidinedione, and a glinide, as well as a GLP-1 agonist and a DPP-4 inhibitor. Suddenly she asks you how much these medications cost.
The cost of health care in general and medications in particular continue to dominate discussions. This is especially true for medications that have arrived on the market more recently, including the GLP-1 agonists and the DPP-4 inhibitors, which range in cost from about $7 to $14 per day.9-12 These agents, however, may be covered by health insurance, so cost to the patient may be limited to copays. The lower risk of hypoglycemia observed with the GLP-1 agonists and DPP-4 inhibitors compared with some other glucose-lowering therapies may make it possible to perform self-monitoring of blood glucose less frequently, but this is an individual patient issue.
Although it may be difficult or uncomfortable to talk about the costs of treatment, it has a great impact on medication adherence and overall treatment satisfaction. In this case, in addition to discussing insurance coverage and what she can afford, you should also talk with the patient about ways the cost of her medications might be reduced.
While no generic formulations are available for exenatide, liraglutide, saxagliptin, or sitagliptin, each manufacturer offers a prescription assistance program. Patients should also be encouraged to check manufacturers’ Web sites for available coupons or discount programs.
With this patient, you also might talk about how different medications can affect total cost of her diabetes treatment differently. Limited retrospective analyses suggest that compared with glimepiride, liraglutide reduces the total cost of care, including care for ocular events and neuropathy leading to amputation.13 Other studies indicate that the overall cost of care with exenatide is lower than with insulin glargine,14 including care for hypoglycemia-related events.15
Summary
Working closely with patients and providing ongoing education, ideally in conjunction with a diabetes care team, can help ensure that the best treatment options are selected for an individual patient and that the patient is capable of effective self-management.
1. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2009.
2. Victoza [package insert]. Princeton, NJ: Novo Nordisk Inc; 2010.
3. Januvia [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; February 2, 2010.
4. Onglyza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
5. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092-1100.
6. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473-481.
7. Nauck M, Frid A, Hermansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84-90.
8. Linnebjerg H, Kothare PA, Skrivanek Z, et al. Exenatide: effect of injection time on postprandial glucose in patients with type 2 diabetes. Diabet Med. 2006;23:240-245.
9. Byetta (exenatide) pen. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=66780021201&trx=1Z5005. Accessed August 18, 2010.
10. Januvia (sitagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/drugindex/rxsearch.asp?drug=Januvia&trx=1Z5005. Accessed August 18, 2010.
11. Onglyza (saxagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00003421521&trx=1Z5006. Accessed August 18, 2010.
12. Victoza (liraglutide) injection. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00169406012&trx=1Z5006. Accessed August 18, 2010.
13. Sullivan SD, Alfonso-Cristancho R, Conner C, et al. A simulation of the comparative long-term effectiveness of liraglutide and glimepiride monotherapies in patients with type 2 diabetes mellitus. Pharmacotherapy. 2009;29:1280-1288.
14. Misurski D, Lage MJ, Fabunmi R, et al. A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine. Appl Health Econ Health Policy. 2009;7:245-254.
15. Fabunmi R, Nielsen LL, Quimbo R, et al. Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine. Curr Med Res Opin. 2009;25:777-786.
1. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2009.
2. Victoza [package insert]. Princeton, NJ: Novo Nordisk Inc; 2010.
3. Januvia [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; February 2, 2010.
4. Onglyza [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
5. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092-1100.
6. Garber A, Henry R, Ratner R, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473-481.
7. Nauck M, Frid A, Hermansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32:84-90.
8. Linnebjerg H, Kothare PA, Skrivanek Z, et al. Exenatide: effect of injection time on postprandial glucose in patients with type 2 diabetes. Diabet Med. 2006;23:240-245.
9. Byetta (exenatide) pen. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=66780021201&trx=1Z5005. Accessed August 18, 2010.
10. Januvia (sitagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/drugindex/rxsearch.asp?drug=Januvia&trx=1Z5005. Accessed August 18, 2010.
11. Onglyza (saxagliptin) tablets. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00003421521&trx=1Z5006. Accessed August 18, 2010.
12. Victoza (liraglutide) injection. Drugstore.com. http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00169406012&trx=1Z5006. Accessed August 18, 2010.
13. Sullivan SD, Alfonso-Cristancho R, Conner C, et al. A simulation of the comparative long-term effectiveness of liraglutide and glimepiride monotherapies in patients with type 2 diabetes mellitus. Pharmacotherapy. 2009;29:1280-1288.
14. Misurski D, Lage MJ, Fabunmi R, et al. A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine. Appl Health Econ Health Policy. 2009;7:245-254.
15. Fabunmi R, Nielsen LL, Quimbo R, et al. Patient characteristics, drug adherence patterns, and hypoglycemia costs for patients with type 2 diabetes mellitus newly initiated on exenatide or insulin glargine. Curr Med Res Opin. 2009;25:777-786.