Question for the group. My sister and I both started semaglutide around the same time. She has T2 diabetes and is on Ozempic 1mg for blood sugar control. I don't have diabetes and I'm on compounded sema 1.7mg purely for weight loss.
She's lost barely 8 lbs in 5 months. I've lost 34 lbs in 6 months.
She's frustrated and honestly a little resentful (understandably). But it got me wondering — does semaglutide work differently in people with T2DM vs people without? Is the weight loss mechanism somehow blunted when your body is also using it for glucose control?
This is actually a really well-studied phenomenon. The short answer is: yes, people with T2DM tend to lose less weight on semaglutide than people without T2DM.
The data is pretty clear:
| Trial | Population | Dose | Mean Weight Loss (68 wks) |
|---|---|---|---|
| STEP 1 | Overweight/obese, no T2DM | 2.4mg | -14.9% |
| STEP 2 | Overweight/obese WITH T2DM | 2.4mg | -9.6% |
| STEP 2 | Overweight/obese WITH T2DM | 1.0mg | -7.0% |
| STEP 3 | Overweight/obese, no T2DM + IBT | 2.4mg | -16.0% |
So at the same 2.4mg dose, non-diabetics lost about 50% more weight than diabetics (14.9% vs 9.6%).[1][2]
Several reasons for this:
- Insulin effects: T2DM patients often have hyperinsulinemia. Insulin is an anabolic hormone that promotes fat storage. As semaglutide improves insulin sensitivity and reduces hyperinsulinemia, you'd think that would help with weight loss — but the metabolic correction itself means the body isn't wasting as many calories through glucosuria (peeing out glucose).
- Concomitant medications: Many T2DM patients are on sulfonylureas or insulin, which cause weight gain. This creates a pharmacological headwind.
- Metabolic adaptation: T2DM involves more profound metabolic derangement — insulin resistance affects adipose tissue metabolism, making it harder to mobilize fat stores.
- Dose differences: Your sister is on 1mg (Ozempic dose), you're on 1.7mg. That's a significant dose difference.
Tell your sister she's not doing anything wrong. The drug is working — it's just working on more things simultaneously in her body. And her A1C improvement is arguably more clinically significant than your weight loss in terms of long-term health outcomes.
[2] Wilding JPH, et al. N Engl J Med. 2021;384(11):989-1002.
Wow that table is eye-opening. 14.9% vs 9.6% at the SAME dose. I had no idea the gap was that big.
My sister IS on metformin and glimepiride. The glimepiride is a sulfonylurea right? So that could be working against her weight loss?
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Shop Reference StandardsYes, glimepiride is a sulfonylurea. They work by stimulating insulin secretion regardless of blood sugar levels, which can cause weight gain and hypoglycemia. Many endocrinologists will discontinue or reduce sulfonylureas when starting a GLP-1 agonist. Your sister should talk to her doctor about whether she still needs it — semaglutide itself stimulates insulin secretion, but in a glucose-dependent manner (so lower hypo risk).
If she can get off the glimepiride, she may see better weight loss results. That's between her and her endo though, NOT medical advice from a forum.
T2DM here, started sema 8 months ago. I can confirm the weight loss is slower for us. I've lost 22 lbs total, which is about 9% of my starting weight. Not as dramatic as the numbers I see non-diabetic people posting, but my A1C went from 8.1 to 5.9 and I'm off 2 of my 3 diabetes meds. That's a HUGE win even if the scale isn't moving as fast.
The cardiovascular benefit is also specifically proven in the diabetic population (SELECT trial showed 20% CV event reduction). So we're getting benefits that don't show up on the scale.