How a diabetes drug became a global obesity therapy

A well-known 'side effect'

Already with the approval of exenatide (Byetta) in 2005 and especially of liraglutide (Victoza) in 2010, it was clear: GLP-1 receptor agonists reduce not only HbA1c but also body weight in type-2-diabetes patients — typically by 2–5 kg. The effect was reproducible and mechanistically explicable: central appetite suppression via the hypothalamus, slowed gastric emptying, modulated satiety signals.

In 2014, Novo Nordisk took the first consistent step: the same substance, liraglutide, was approved at a higher dose (3.0 mg instead of 1.8 mg) as Saxenda for the obesity indication. Weight loss was around 5–8% — moderate but statistically robust versus placebo. Communication remained restrained: daily injection, moderate effect, high cost.

Semaglutide: same drug, different magnitude

Semaglutide was approved in 2017 under the name Ozempic for type-2 diabetes — weekly subcutaneous injection, higher potency than liraglutide. Already in the SUSTAIN trials for the diabetes indication, weight loss was strikingly strong: 4–6 kg over 30–56 weeks. Novo Nordisk decided to set up the obesity programme separately — the STEP series (Semaglutide Treatment Effect in People with obesity).

STEP-1 was published in 2021 (NEJM, Wilding et al.). 1,961 adults without diabetes, BMI ≥ 30 (or ≥ 27 with comorbidity). 68 weeks of treatment with 2.4 mg semaglutide s.c. weekly vs. placebo, each plus lifestyle intervention. Result: average weight loss of 14.9% in the semaglutide arm vs. 2.4% in the placebo arm. About a third of those treated lost more than 20% of baseline weight. That was a different order of magnitude than anything previously achievable pharmacologically.

The market pivot and collision with reality

In June 2021 semaglutide 2.4 mg was FDA-approved under the name Wegovy for obesity. What followed was not a marketing success in the classical sense — it was a cultural phenomenon: reports from Hollywood, social media, hashtag trends. Within 18 months, global demand and Novo Nordisk's limited production capacity collided so hard that there were months-long supply shortages for both Wegovy and Ozempic — the latter directly affecting diabetes patients dependent on the drug.

Eli Lilly followed in 2022 with tirzepatide (Mounjaro) — dual GLP-1/GIP agonist, documented in SURMOUNT-1 (2022) with even stronger weight loss (up to 22.5% at 15 mg). In 2023, tirzepatide was FDA-approved under the name Zepbound for obesity. A second, mechanistically extended wave was opened.

What the pivot story shows — and what it does not

Three observations from this series are interesting for scientific assessment. First: the obesity effect was not a new mechanism promise but a consistent dose escalation of a known drug in a dedicated indication trial. Second: the clinical effect is real and well documented by a large, randomised, multicentre trial series with several thousand participants. Third: long-term data — cardiovascular endpoints (SELECT trial 2023, MACE reduction in obese patients without diabetes), maintenance of weight loss over several years, off-treatment rebound — remain partially incomplete.

What the story does not show: that Wegovy or tirzepatide are simple solutions for complex metabolic conditions. The trials document effect sizes under optimal compliance, medical supervision and lifestyle co-intervention. Real-world care settings are more heterogeneous; discontinuation rates and weight regain after treatment cessation are substantial.

Open questions

• How durable is weight loss after treatment ends? STEP-4 data and observational cohorts suggest substantial rebound effects.
• What long-term safety signals emerge over 10+ years? Pancreatitis, gallbladder and thyroid markers are under observation.
• How does global diffusion of these substances change public-health strategies for obesity — and who bears the cost?
• Which effect of the GLP-1/GIP line is mechanistic (central satiety) and which is societal (changed eating behaviour while on treatment)?