Episode 61: Semaglutide for Obesity.  

Dr Arreaza discusses with Dr Carranza the results of the STEP trials: Semaglutide Treatment Effect in People with obesity, which allowed semaglutide gain FDA approval as a treatment for obesity.

By Hector Arreaza, MD, and Claudia Carranza, MD

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

One of the major challenges of modern medicine is to find an effective treatment for obesity.

Obesity was considered a disease in 1998 by the National Institutes of Health[1].

In 2002, the Internal Revenue Service, AKA the feared IRS, issued a statement to make obesity treatment a deductible medical expense. Who would have known that obesity was tax deductible?

Later, in 2013 obesity was accepted as a complex, chronic disease by the American Medical Association[2]. Many other organizations have made statements in favor or against the definition of obesity as a disease.

We recently announced the exciting news of semaglutide as a new FDA-approved medication for the chronic treatment of obesity. Today we want to give you a very brief summary (brief-ísimo) of the trials that allowed semaglutide to gain that FDA-approval. 

Semaglutide was tested at different levels with the STEP trials. STEP stands for Semaglutide Treatment Effect in People with obesity (STEP). All these trials were done in 68 weeks, all patients received counseling about lifestyle modifications, 70-80% were women, ages averaging 40-50 years old.

STEP 1: Does semaglutide cause weight loss in patients without diabetes?

The focal point of this trial was weight management with semaglutide in patients without diabetes. This was a double-blind trial. There were 1961 participants enrolled. A group was assigned to placebo and another group was assigned to weekly injection of semaglutide. For the semaglutide group, the goal dose of semaglutide was 2.4 mg, starting with 0.25 mg, increasing every 4 weeks: 0.5 -> 1.0 -> 1.7 -> 2.4 (reaching the goal dose in 4 months), 3 out of 4 participants were Caucasians. 

Outcomes: after 68 weeks weight reduction was -16.9% in patients on semaglutide, more than 86% of participants had a weight loss >5%, 69% lost >10% of their weight, and 50% percent lost >15% of their body weight, and about 32% lost >20% of their weight. This may be comparable to bariatric surgery in some patients; however, the weight loss is not as dramatic. Other parameters improved were waist circumference, blood pressure, triglycerides. LDL and total cholesterol were not significantly affected. There was a clinical meaningful change in 40% of patients. 7 out of 100 could not complete trial for GI adverse effects, most commonly nausea, diarrhea, vomiting, constipation. Acute pancreatitis presented in 0.2% of the semaglutide group (all recovered during study) vs 0% in the placebo group[3]. 

STEP 2: Does semaglutide cause weight loss in patients with diabetes? 

The focal point of this study was weight management with semaglutide in type 2 diabetes mellitus. 1210 patients participated in 12 different countries across Europe, North America, South America, the Middle East, South Africa, and Asia. Patients were randomly assigned to semaglutide 2.4 mg weekly, Semaglutide 1 mg weekly, or placebo. 

Weight loss was superior with semaglutide 2.4 mg, -9.6% of body weight with semaglutide vs -3.4% weight loss with placebo. As you can see, weight loss in individuals with diabetes is more difficult. The effect on diabetes control was about the same with semaglutide 1 mg vs 2.4 mg. The 1 mg dose reduced A1C -1.5%, and the reduction was -1.6% with semaglutide 2.4 mg. A1C reduction was about the same regardles