Dulaglutide vs semaglutide

Two weekly GLP-1 drugs from rival companies — how far apart are they?

Direct head-to-head trial exists
In one paragraphThey were compared directly in SUSTAIN 7: semaglutide lowered HbA1c and weight more than dulaglutide at matched doses in type 2 diabetes. Both have cardiovascular-outcome trials in diabetes, and dulaglutide's REWIND covered the broadest population — nearly 10,000 people, most without prior heart disease. Semaglutide is also approved for weight management and has an outcomes trial in obesity without diabetes; dulaglutide is a diabetes drug with modest weight effects.

Side by side

A DulaglutideA Semaglutide
LYO gradeAA
Head-to-head HbA1c, 40 wkSUSTAIN 7, n=1,201−1.1 / −1.4 points (0.75 / 1.5 mg)−1.5 / −1.8 points (0.5 / 1.0 mg)
Head-to-head weight, 40 wkSUSTAIN 7−2.3 / −3.0 kg−4.6 / −6.5 kg
Cardiovascular outcomes trialREWIND: 12% relative MACE reduction, n=9,901, 5.4 yr, mostly without prior CVDSUSTAIN-6 (diabetes) and SELECT: 20% relative MACE reduction in obesity without diabetes, n=17,604
Approved for weight managementNoYes (2.4 mg, Wegovy)
MoleculeTwo GLP-1 analogue chains fused to an antibody Fc fragmentGLP-1 analogue with a fatty-acid side chain
First approval20142017
Oral formNoYes (Rybelsus)
Verdict

Semaglutide for weight and for glucose, on direct evidence. Dulaglutide holds its own on cardiovascular protection in diabetes and is the drug for people who need a GLP-1 without the weight-loss dose. Neither is a grey-market compound; both are prescription-only.

The direct trial

SUSTAIN 7 randomised 1,201 adults with type 2 diabetes on metformin to semaglutide 0.5 or 1.0 mg or dulaglutide 0.75 or 1.5 mg for 40 weeks. Semaglutide won on both endpoints at each dose level: larger HbA1c reductions and roughly twice the weight loss. Gastrointestinal disorders were the most common adverse event in every arm — 43–44% on semaglutide, 33% and 48% on the two dulaglutide doses — and the most common reason for stopping either drug.

Where dulaglutide's evidence is strongest

REWIND is the reason dulaglutide is not simply the weaker drug. It enrolled 9,901 people with type 2 diabetes, more than two-thirds of whom had risk factors but no prior cardiovascular disease, and followed them for a median of 5.4 years — the longest and broadest GLP-1 outcomes trial. The 12% relative reduction in major events is smaller than semaglutide's 20% in SELECT, but the populations differ: SELECT enrolled people with existing cardiovascular disease and no diabetes.

Weight

Dulaglutide is not a weight-loss drug. Its diabetes doses produce a few kilograms; the higher 3 mg and 4.5 mg doses add a little more. Semaglutide at 2.4 mg produced 14.9% loss at 68 weeks in STEP 1 and is approved for that use. Someone asking which is better for weight is asking a question the trials have already answered.

Questions people actually ask

Is dulaglutide weaker than semaglutide?
For glucose and weight, yes, in the direct trial. For cardiovascular protection in diabetes both work; the trials are not directly comparable.
Why would anyone choose dulaglutide?
A single-use pen with no dose titration for many patients, a long cardiovascular record in people without prior heart disease, and less weight loss where that is not wanted.
Are they the same class of side effect?
Yes: nausea, diarrhoea, vomiting and constipation during dose escalation, rare pancreatitis and gallbladder events, and the rodent thyroid warning.

References

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