Obesity Case 11

A 63-year-old African American male with a history of obesity, T2DM, CKD3b and recent NSTEMI was referred for cardiometabolic risk optimization.

Medications: atorvastatin 80mg, lisinopril 20mg, aspirin 162mg, metformin 1000mg bid, metoprolol 50mg daily, duloxetine 20mg daily

Diet:

  1. Heavy in starchy and refined carbohydrates, “meat & potatoes,” and casseroles
  2. Doesn’t snack much and avoids sweets or baked goods during the day and evening but eats fruit for dessert
  3. No sugar-sweetened beverages and rare alcohol

Exercise: states he has always been physically active with his work but has been in cardiac rehab three times weekly for the past 6 weeks

Sleep: has OSA treated with cpap

Exam: BMI 37 and waist circumference 111cm; BP 140/90; pulse 66

Labs: HbA1c 7.6%, eGFR 44, total cholesterol 145, HDLc 45 mg/dL, trig 160 mg/dL, LDLc 68 mg/dL, albumin 4, ALT 35, platelets 300,000, urine albumin:creatinine 320

Question 1

In addition to adding a SGLT2inh for cardiovascular and renal benefits, which medication approved for the chronic therapy of obesity would be preferred?

A. Naltrexone/bupropion ER
B. Liraglutide 3mg
C. Phentermine/topiramate ER
D. Orlistat
Incorrect!
Correct!
Correct Answer
B. Liraglutide 3mg

The GLP-1 analog, liraglutide, previously approved for the treatment of type 2 diabetes mellitus (T2DM), is also approved as a weight loss agent at a dose of 3 mg daily. In the SCALE diabetes trial, there was an average of about 4% placebo-subtracted weight loss and HbA1c reduction of 1% more than placebo and statistically better in both regards than the 1.8-mg dosing[1]. Liraglutide at all doses consistently improves cardiometabolic risk factors including lipids and blood pressure with slightly increased heart rate. A pooled post hoc analysis of the phase 3 trials involving liraglutide 3 mg suggested possible cardiovascular benefit but with small numbers of events and wide confidence intervals[2]. Further reassurance of cardiovascular safety, and perhaps benefit, could be drawn from the benefits shown in the LEADER trial of 1.8-mg liraglutide in patients with T2DM and high-risk (and high prevalence of established) CVD[3].

The other medications are not preferred for reducing CV risk in this patient with established ascvd and CKD3b though could be considered[4]. Orlistat reduces cardiovascular risk factors and has no cardiovascular safety concerns but has not shown cardiovascular event reduction and is not as beneficial for this patients glycemic control and renal benefits. Sympathomimetics, like phentermine in the combination of phentermine/topiramate ER, are to be used in caution for patients at increased cardiovascular risk. While the cardiovascular safety of phentermine/topiramate ER is not established, data from the phase 3 trials are reassuring thus far[5]. Weight loss with naltrexone/bupropion ER is accompanied by improvements of several cardiometabolic parameters, though blood pressure generally remained higher than placebo in trials. A cardiovascular outcome trial was initiated for naltrexone/bupropion ER with reassuring early data, though with high discontinuation rate, but the trial had to be terminated due to public compromise of that data; thus, the cardiovascular safety has not been determined[6].

 

[1] Davies MJ, et al. Efficacy of liraglutide for weight loss among patients with type 2

diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 2015;314(7):687–699

[2] Davies MJ, et al. Liraglutide and cardiovascular outcomes in adults with overweight

or obesity: a post hoc analysis from SCALE randomized controlled trials. Diabetes Obes

Metab 2018;20:734–739

[3] Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J

Med 2016;375(4):311–322.

[4]Garvey WT, et al. American Association of Clinical Endocrinologists and American

College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care

of Patients with Obesity. Endocr Pract 2016;22(suppl 3):1–203

[5] Ritchey ME, et al. Cardiovascular safety during and after use of phentermine and

topiramate. J Clin Endocrinol Metab 2019;104(2):513–522. doi:10.1210/jc.2018-01010.

[6] Nissen SE, et al. Effect of naltrexone-bupropion on major adverse cardiovascular

events in overweight and obese patients with cardiovascular risk factors: a randomized

clinical trial. JAMA 2016;315(10):990–1004

The GLP-1 analog, liraglutide, previously approved for the treatment of type 2 diabetes mellitus (T2DM), is also approved as a weight loss agent at a dose of 3 mg daily. In the SCALE diabetes trial, there was an average of about 4% placebo-subtracted weight loss and HbA1c reduction of 1% more than placebo and statistically better in both regards than the 1.8-mg dosing[1]. Liraglutide at all doses consistently improves cardiometabolic risk factors including lipids and blood pressure with slightly increased heart rate. A pooled post hoc analysis of the phase 3 trials involving liraglutide 3 mg suggested possible cardiovascular benefit but with small numbers of events and wide confidence intervals[2]. Further reassurance of cardiovascular safety, and perhaps benefit, could be drawn from the benefits shown in the LEADER trial of 1.8-mg liraglutide in patients with T2DM and high-risk (and high prevalence of established) CVD[3].

The other medications are not preferred for reducing CV risk in this patient with established ascvd and CKD3b though could be considered[4]. Orlistat reduces cardiovascular risk factors and has no cardiovascular safety concerns but has not shown cardiovascular event reduction and is not as beneficial for this patients glycemic control and renal benefits. Sympathomimetics, like phentermine in the combination of phentermine/topiramate ER, are to be used in caution for patients at increased cardiovascular risk. While the cardiovascular safety of phentermine/topiramate ER is not established, data from the phase 3 trials are reassuring thus far[5]. Weight loss with naltrexone/bupropion ER is accompanied by improvements of several cardiometabolic parameters, though blood pressure generally remained higher than placebo in trials. A cardiovascular outcome trial was initiated for naltrexone/bupropion ER with reassuring early data, though with high discontinuation rate, but the trial had to be terminated due to public compromise of that data; thus, the cardiovascular safety has not been determined[6].

 

[1] Davies MJ, et al. Efficacy of liraglutide for weight loss among patients with type 2

diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 2015;314(7):687–699

[2] Davies MJ, et al. Liraglutide and cardiovascular outcomes in adults with overweight

or obesity: a post hoc analysis from SCALE randomized controlled trials. Diabetes Obes

Metab 2018;20:734–739

[3] Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J

Med 2016;375(4):311–322.

[4]Garvey WT, et al. American Association of Clinical Endocrinologists and American

College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care

of Patients with Obesity. Endocr Pract 2016;22(suppl 3):1–203

[5] Ritchey ME, et al. Cardiovascular safety during and after use of phentermine and

topiramate. J Clin Endocrinol Metab 2019;104(2):513–522. doi:10.1210/jc.2018-01010.

[6] Nissen SE, et al. Effect of naltrexone-bupropion on major adverse cardiovascular

events in overweight and obese patients with cardiovascular risk factors: a randomized

clinical trial. JAMA 2016;315(10):990–1004