Short answer: Glimepiride (Amaryl) is a sulfonylurea taken once a day with breakfast; metformin is a biguanide taken with meals.12 The glimepiride label reports one trial against metformin, in 272 children aged 8 to 17. After 24 weeks it did not show a similar HbA1c drop, and weight rose more on glimepiride. That label does not recommend glimepiride for children.
| Glimepiride (Amaryl) | Metformin | |
|---|---|---|
| Drug class | Sulfonylurea1 | Biguanide2 |
| Approved for | Adults with type 2 diabetes1 | Adults and children 10 and older with type 2 diabetes2 |
| Starting dose | 1 or 2 mg once daily with breakfast; 1 mg at higher risk of low blood sugar1 | 500 mg twice a day or 850 mg once a day, with meals2 |
| Maximum | 8 mg once daily1 | 2,550 mg a day for adults2 |
| HbA1c change, children new to treatment, 24 weeks | −1.0 points1 | −1.2 points1 |
| Weight change, children, 24 weeks | +2.0 kg1 | +0.7 kg1 |
| Blood sugar below 36 mg/dL, children | 4%1 | 1%1 |
| Common side effects, adults | Headache 8.2% vs 7.8% on placebo; dizziness 5% vs 2.4%1 | Diarrhea 53% vs 12% on placebo; nausea or vomiting 26% vs 8%2 |
| Missed dose | No rule in the label1 | Take the next dose as prescribed; no extra dose the next day2 |
| Boxed warning | None1 | WARNING: LACTIC ACIDOSIS2 |
A single-blind, 24-week trial randomized 272 children aged 8 to 17 with type 2 diabetes to glimepiride (started at 1 mg, mean last dose 4 mg) or metformin (started at 500 mg twice daily, mean last dose 1,365 mg). The overall HbA1c difference was 0.2% in favor of metformin, and the label says the trial "did not meet its primary objective" of showing a similar drop with glimepiride. Weight rose 2.0 kg on glimepiride vs 0.7 kg on metformin.1
The label says glimepiride is not recommended in children because of its effects on body weight and low blood sugar.1 Metformin is approved from age 10.2 The trial was in children; neither label reports a trial of the two in adults.
Glimepiride's label warns of severe low blood sugar, serious allergic reactions, red blood cell breakdown in G6PD deficiency and the sulfonylurea class warning on heart-related deaths from the UGDP study; it can also cause weight gain.1 Metformin's label warns of lactic acidosis, lower vitamin B12 and a higher chance of low blood sugar when added to insulin or a sulfonylurea; it is not used with an eGFR below 30.2 The adult side-effect rows come from each label's own trials. These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison.
Which, if either, fits is for your prescriber. More detail: glimepiride side effects, metformin side effects, the glimepiride and metformin dosing schedules, the metformin missed-dose page, the glimepiride and metformin guides, and Glimepiride vs glipizide: how do the two sulfonylureas differ?.