GLP‑1 news from 2021
21 dated, sourced GLP-1 developments from 2021: approvals, trial results, prices, lawsuits, compounding and culture.
- Business
Novo Nordisk agrees to buy Dicerna Pharmaceuticals for $3.3 billion
The RNA interference specialist was Novo Nordisk's largest acquisition to that point, at $38.25 a share.
- FDA & regulation
Lilly files the Mounjaro new drug application
Eli Lilly submitted NDA 215866 for tirzepatide injection in type 2 diabetes on September 14, 2021; FDA recorded receipt September 15.
- Research
The Obesity Society publishes the definitive supplement review: 16 of 315 trials
Batsis and colleagues screen 20,504 citations and analyze 315 randomized controlled trials of dietary supplements and alternative therapies for weight loss. Only 52 are low risk of bias and sufficient to support efficacy, and of those only 16 show a significant weight difference, ranging from 0.3 to 4.93 kg. The accompanying TOS Clinical Committee perspective urges clinicians to steer patients toward tested approaches.
- Research
SUSTAIN FORTE supports the Ozempic 2 mg dose
Semaglutide 2.0 mg lowered HbA1c 2.2 points versus 1.9 points for 1.0 mg, with 6.9 kg versus 6.0 kg of weight loss and similar tolerability.
- Research
SURPASS-2 puts tirzepatide head-to-head against semaglutide 1 mg
In 1,879 adults with type 2 diabetes on metformin, all three tirzepatide doses beat semaglutide 1 mg on HbA1c (differences -0.15 to -0.45 points) and weight (-1.9 to -5.5 kg). The comparator was the 1 mg diabetes dose, not the 2.4 mg obesity dose, a distinction often lost in secondary coverage.
- Research
SURPASS-1 shows tirzepatide monotherapy cuts HbA1c by about two points
The first tirzepatide phase 3 registration trial, in 478 drug-naive adults with type 2 diabetes, reported HbA1c reductions of 1.87 to 2.07 percentage points versus a 0.04-point rise on placebo, with 31% to 52% of participants reaching an HbA1c below 5.7%.
- FDA & regulation
FDA approves Wegovy for chronic weight management
The FDA approved Wegovy (semaglutide) injection 2.4 mg for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. It was the first new obesity drug approval since 2014 and the first semaglutide product indicated for weight loss.
- Science
GIP receptor agonism shown to sensitize to insulin without weight loss
Samms et al. publish in JCI that tirzepatide raises the glucose infusion rate 1.7-fold in obese GLP-1-receptor-null mice that lose no weight, tracing the effect to glucose disposal into white adipose tissue.
- Culture
S-LITE shows exercise plus a GLP-1 beats either alone on body composition
The S-LITE randomized trial compared placebo, liraglutide, supervised exercise, and exercise plus liraglutide for one year after a low-calorie diet phase. The combination roughly doubled the reduction in body-fat percentage versus either single treatment and preserved lean mass. It remains the only randomized trial directly testing structured exercise alongside a GLP-1 drug with long follow-up.
- Science
Brain GIP receptors shown to be required for dual agonist advantage
A Cell Metabolism study shows mice lacking GIP receptors in the central nervous system are protected from diet-induced obesity and that a GLP-1/GIP dual agonist loses its superiority over a GLP-1 agonist in those animals.
- Research
STEP 4 shows what happens when semaglutide is withdrawn after titration
JAMA published the STEP 4 randomized withdrawal trial. Participants who had already titrated to semaglutide 2.4 mg were randomized to continue or switch to placebo, with lifestyle support maintained in both arms. Over 48 weeks the continuers lost a further 7.9% of body weight while the placebo group gained 6.9%, a difference of 14.8 percentage points, with waist circumference, blood pressure and physical functioning splitting the same way. STEP 4 established the design template every later maintenance trial has used.
- Research
Novo reports that semaglutide 2.4 mg maintains weight loss over 68 weeks
Novo Nordisk released data showing adults with obesity who started semaglutide 2.4 mg achieved and then maintained substantial weight loss across a 68-week trial. The findings supported the pending US application for a weight-management indication.
- Research
STEP 1 publishes the weight-loss curve that anchors every 'how fast does it work' question
The New England Journal of Medicine published STEP 1: 1,961 adults without diabetes, mean weight change -14.9% with semaglutide 2.4 mg at week 68 versus -2.4% with placebo. The responder distribution behind that mean — 86.4% reaching 5%, 69.1% reaching 10%, 50.5% reaching 15%, 32.0% reaching 20% — became the reference point for consumer expectations about pace and distribution of results.
- Research
STEP 2 shows smaller weight loss in people with type 2 diabetes
Semaglutide 2.4 mg produced 9.6% weight loss in adults with type 2 diabetes versus 3.4% on placebo, establishing the consistent diabetes efficacy gap.
- Research
STEP 3 reaches 16.0% weight loss with intensive behavioral therapy
Adding 30 counseling visits and an initial low-calorie diet to semaglutide produced the largest average weight loss in the original STEP program.
- Research
STEP 1 published: 14.9% average weight loss with semaglutide 2.4 mg
The New England Journal of Medicine published the STEP 1 trial, in which adults with obesity taking once-weekly semaglutide 2.4 mg lost an average of 14.9% of body weight over 68 weeks versus 2.4% on placebo. The result reset expectations for what a weight-loss drug could do.
- Business
AWARD-11 adds 3 mg and 4.5 mg doses to Trulicity
In 1,842 patients, dulaglutide 4.5 mg lowers A1C by 1.77 percentage points versus 1.54 with 1.5 mg, and produces 1.6 kg more weight loss. The gains are real but small, and the trial shows dose escalation cannot close the gap with semaglutide.
- Science
Study quantifies how much semaglutide cuts food intake
In a randomized crossover study, adults with obesity on semaglutide 2.4 mg ate 35% less at a free-access lunch than on placebo, with lower hunger and fewer food cravings. Gastric emptying was barely changed, pointing to the brain as the main driver.