The SURMOUNT-2 study demonstrates that tirzepatide is equally effective in patients combining type 2 diabetes and obesity, with major glycemic benefits.
After the spectacular results of SURMOUNT-1 in non-diabetic patients, the question arose: would tirzepatide be as effective in patients simultaneously presenting with type 2 diabetes and obesity? The SURMOUNT-2 study, published in The Lancet in 2023, provides a clear and positive answer.
Study Population and Design
SURMOUNT-2 recruited 938 adults with type 2 diabetes (HbA1c between 7% and 10%) and a BMI ≥ 27 kg/m². Participants were randomized to receive tirzepatide at 10 mg, 15 mg, or placebo for 72 weeks. Unlike SURMOUNT-1, all patients were taking one or more oral antidiabetic drugs (mainly metformin).
The primary endpoint was the percentage change in body weight at 72 weeks. Secondary endpoints included HbA1c, waist circumference, blood pressure, and lipid profile.
Weight Loss in Diabetic Patients
The results of SURMOUNT-2 confirm the efficacy of tirzepatide in this more complex population:
- Tirzepatide 10 mg: 12.8% weight loss (vs 3.2% with placebo)
- Tirzepatide 15 mg: 14.7% weight loss
These figures are slightly lower than those of SURMOUNT-1 (19-21%), which was expected. Diabetic patients generally lose less weight with GLP-1 treatments due to insulin resistance and the longer duration of their metabolic disease. Nevertheless, a 14.7% loss remains a remarkable result, surpassing semaglutide in diabetic patients (STEP-2 study: 9.6%).
Exceptional Glycemic Improvement
Beyond weight, SURMOUNT-2 revealed major glycemic benefits:
- HbA1c reduction: -2.1% at 10 mg and -2.4% at 15 mg (vs -0.5% with placebo)
- Proportion achieving HbA1c < 5.7% (normoglycemia): 44% at 10 mg and 52% at 15 mg
- Fasting glucose: reduction of 2.2 to 2.7 mmol/L
The fact that more than half of patients at the 15 mg dose achieved an HbA1c in the non-diabetic range is a remarkable result. This suggests that tirzepatide could induce remission of type 2 diabetes in some patients, particularly those with a recent diagnosis.
Cardiometabolic Benefits
SURMOUNT-2 also documented significant improvements in cardiovascular risk factors, a critical issue in diabetic patients:
- Systolic blood pressure: -5 to -8 mmHg
- Triglycerides: -19 to -25%
- HDL cholesterol: +6 to +8%
- Waist circumference: -10 to -12 cm
- C-reactive protein (inflammation): significant reduction
These data reinforce the positioning of tirzepatide as a global metabolic treatment, and not simply an antidiabetic or anti-obesity medication.
Tolerance Profile Specific to Diabetic Patients
The side effects observed in SURMOUNT-2 are comparable to those in SURMOUNT-1, with some specificities related to diabetes:
- Nausea: 18-26% (slightly less than in SURMOUNT-1, possibly due to concomitant treatments)
- Diarrhea: 14-21%
- Hypoglycemia: rare (< 1%) thanks to the glucose-dependent action of tirzepatide
- Discontinuation rate due to adverse events: 3-7%
The low rate of hypoglycemia is a major advantage compared to sulfonylureas and insulin, often used in type 2 diabetes. Tirzepatide allows for intensification of antidiabetic treatment without increasing the risk of hypoglycemia.
Practical Implications for Patients
The results of SURMOUNT-2 have several practical implications. First, they confirm that obese diabetic patients do not need to choose between treating their diabetes and losing weight: tirzepatide does both simultaneously. Second, they suggest that early and aggressive management of obesity in diabetic patients could alter the natural history of the disease.
To maximize treatment benefits, regular monitoring of blood glucose, weight, and metabolic parameters is essential. The MounjaGO application integrates weight and symptom tracking and allows for the generation of detailed PDF reports for each medical consultation.
FAQ: SURMOUNT-2 Study
Why is weight loss lower in diabetic patients?
Patients with type 2 diabetes generally have more marked insulin resistance and a longer metabolic disease duration. Some concomitant antidiabetic treatments (such as sulfonylureas) can also promote weight gain, partially counteracting the effect of tirzepatide.
Can tirzepatide replace insulin in diabetic patients?
In some cases, yes. Patients on basal insulin alone who switch to tirzepatide can often stop insulin under medical supervision. However, patients on multiple daily insulin injections require a gradual transition and close monitoring of blood glucose.
Can tirzepatide be combined with metformin?
Yes, this is even the most common combination. In SURMOUNT-2, the majority of patients were taking metformin in combination. This combination is well tolerated and offers complementary benefits.