Short answer: Metformin is a generic tablet taken with meals once to three times a day; Ozempic (semaglutide) is a once-weekly injection. Both are approved, with diet and exercise, to lower blood sugar in type 2 diabetes, and Ozempic is also approved to lower heart and kidney risks in some adults.12 Their label trials did not compare them, and many Ozempic trial patients also took metformin.
| Metformin (tablets) | Ozempic (semaglutide) | |
|---|---|---|
| Drug class | Biguanide1 | GLP-1 receptor agonist2 |
| Form | Tablets of 500 mg, 850 mg and 1,000 mg1 | Prefilled pen, injected under the skin of the abdomen, thigh or upper arm once a week2 |
| Approved for | Blood sugar in type 2 diabetes, adults and children 10 and older1 | Blood sugar in adults with type 2 diabetes; lowering heart attack, stroke and cardiovascular death in those with heart disease; lowering kidney decline in those with chronic kidney disease2 |
| Label dosing (adults) | Start 500 mg twice a day or 850 mg once a day with meals; raise by 500 mg weekly or 850 mg every 2 weeks; up to 2,550 mg a day1 | 0.25 mg weekly for 4 weeks, then 0.5 mg; may go to 1 mg and then 2 mg, each after at least 4 weeks2 |
| Half-life | About 6.2 hours in plasma, about 17.6 hours in whole blood1 | about 7 days (label: about 1 week; present for about 5 weeks after the last dose)2 |
| Kidney rules | Not used if eGFR is under 30; not started if eGFR is 30 to 451 | No dose change for kidney impairment2 |
| Boxed warning | Lactic acidosis1 | Thyroid C-cell tumors seen in rodents2 |
| Label trial on its own vs placebo | 29 weeks: HbA1c −1.4 vs +0.4 points on placebo1 | 30 weeks: HbA1c −1.4 (0.5 mg) and −1.6 (1 mg) vs −0.1 points on placebo2 |
| Weight in that trial | −1.4 lb vs −2.4 lb on placebo at 29 weeks1 | −3.8 kg (0.5 mg) and −4.7 kg (1 mg) vs −1.2 kg on placebo at 30 weeks2 |
| Most common side effects | Diarrhea 53% vs 12% on placebo; nausea or vomiting 26% vs 8%1 | Nausea 15.8% (0.5 mg) and 20.3% (1 mg) vs 6.1% on placebo; diarrhea 8.5% and 8.8% vs 1.9%2 |
Not in the labels. Each label reports its own trial against placebo in people managing type 2 diabetes with diet and exercise alone. In the metformin trial, HbA1c fell 1.4 points over 29 weeks vs a 0.4-point rise on placebo.1 In the Ozempic monotherapy trial of 388 adults, HbA1c fell 1.4 points on 0.5 mg and 1.6 points on 1 mg over 30 weeks vs 0.1 on placebo.2
These numbers come from separate placebo-controlled trials with different people, lengths and methods, so they are not a head-to-head comparison. Starting HbA1c was 8.4% in the metformin trial and about 8.1% in the Ozempic trial.12
Often, in the trials. Ozempic was tested on top of metformin in several label trials: for example, in a 56-week trial of 1,231 adults where 94% took metformin, and in a 30-week trial against insulin glargine where people took metformin with or without a sulfonylurea.2 The metformin label notes a higher risk of low blood sugar only when it is combined with insulin or drugs that push the pancreas to release insulin.1 Whether to combine them is a decision for you and your prescriber.
Ozempic has two outcome approvals that the metformin label does not. In SUSTAIN 6, 3,297 adults with type 2 diabetes and heart disease had heart attack, stroke or cardiovascular death in 6.6% on Ozempic vs 8.9% on placebo (hazard ratio 0.74). In FLOW, in adults with type 2 diabetes and chronic kidney disease, the main kidney and heart composite had a hazard ratio of 0.76.2
More detail: Ozempic side effects, the Ozempic dosing schedule, what to do if you miss an Ozempic dose, how to store Ozempic, and the Metformin and Semaglutide guides.