Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A Systematic Review and Network Meta-analysis

Rohan Khera, Ambarish Pandey, Apoorva K. Chandar, Mohammad H. Murad, Larry J. Prokop, Ian J. Neeland, Jarett D. Berry, Michael Camilleri, Siddharth Singh

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Abstract

Background & Aims: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults. Methods: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration−approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results: In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m2), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, –4.4 to –3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, –3.5 to –3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors. Conclusions: In a systematic review and network meta-analysis, we found Food and Drug Administration−approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications. PROSPERO: CRD42016039486.

Original languageEnglish (US)
Pages (from-to)1309-1319.e7
JournalGastroenterology
Volume154
Issue number5
DOIs
StatePublished - Apr 1 2018

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Waist Circumference
Blood Glucose
Weight Loss
Fasting
Phentermine
Anti-Obesity Agents
Bupropion
Naltrexone
Hemoglobins
Cholesterol
HDL Cholesterol
Randomized Controlled Trials
Placebos
Confidence Intervals
Food
United States Food and Drug Administration
HDL Lipoproteins
LDL Lipoproteins
Pharmaceutical Preparations
LDL Cholesterol

Keywords

  • BMI
  • Heart Disease
  • Pharmacotherapy
  • Vascular

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles : A Systematic Review and Network Meta-analysis. / Khera, Rohan; Pandey, Ambarish; Chandar, Apoorva K.; Murad, Mohammad H.; Prokop, Larry J.; Neeland, Ian J.; Berry, Jarett D.; Camilleri, Michael; Singh, Siddharth.

In: Gastroenterology, Vol. 154, No. 5, 01.04.2018, p. 1309-1319.e7.

Research output: Contribution to journalArticle

Khera, Rohan ; Pandey, Ambarish ; Chandar, Apoorva K. ; Murad, Mohammad H. ; Prokop, Larry J. ; Neeland, Ian J. ; Berry, Jarett D. ; Camilleri, Michael ; Singh, Siddharth. / Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles : A Systematic Review and Network Meta-analysis. In: Gastroenterology. 2018 ; Vol. 154, No. 5. pp. 1309-1319.e7.
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abstract = "Background & Aims: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults. Methods: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration−approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results: In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m2), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95{\%} confidence interval, –4.4 to –3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95{\%} confidence interval, –3.5 to –3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors. Conclusions: In a systematic review and network meta-analysis, we found Food and Drug Administration−approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications. PROSPERO: CRD42016039486.",
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AU - Murad, Mohammad H.

AU - Prokop, Larry J.

AU - Neeland, Ian J.

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N2 - Background & Aims: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults. Methods: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration−approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results: In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m2), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, –4.4 to –3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, –3.5 to –3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors. Conclusions: In a systematic review and network meta-analysis, we found Food and Drug Administration−approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications. PROSPERO: CRD42016039486.

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KW - BMI

KW - Heart Disease

KW - Pharmacotherapy

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