Tirzepatide: A Promising Alternative for Type 2 Diabetes Management

A recent study reveals tirzepatide as a highly effective and safer alternative to prandial insulin for individuals with type 2 diabetes inadequately controlled by basal insulin. This study was published in JAMA Network by Rosenstock J. and colleagues. The findings showcase substantial improvements in glycemic control, significant weight loss, and reduced hypoglycemia risk, potentially revolutionizing the treatment landscape for diabetes.

Tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown remarkable efficacy and safety in comparison to prandial insulin as an adjunctive therapy to basal insulin for individuals with type 2 diabetes.

The SURPASS-6 Phase 3b Clinical Trial

The SURPASS-6 phase 3b clinical trial, conducted at 135 sites across 15 countries, enrolled 1428 adults with type 2 diabetes to evaluate the effects of tirzepatide. Participants, already taking basal insulin, were randomly assigned to receive once-weekly subcutaneous injections of tirzepatide at three different doses (5 mg, 10 mg, or 15 mg) or prandial thrice-daily insulin lispro.

Study Outcomes

The primary outcome of the study was to establish the noninferiority of tirzepatide when compared to insulin lispro, both as additional treatments to insulin glargine, in terms of HbA1c change from baseline at week 52. The noninferiority margin was set at 0.3%. Key secondary endpoints included the change in body weight and the percentage of participants achieving an HbA1c target of less than 7.0%.

Results

• At week 52, tirzepatide demonstrated superior glycemic control with an estimated mean change from baseline in HbA1c of -2.1%, compared to -1.1% with insulin lispro. This resulted in mean HbA1c levels of 6.7% with tirzepatide, compared to 7.7% with insulin lispro.
• The change in body weight was significantly different between the two groups, with tirzepatide leading to a substantial reduction of -9.0 kg compared to an increase of 3.2 kg with insulin lispro.
• The percentage of participants achieving an HbA1c of less than 7.0% was notably higher with tirzepatide, at 68%, compared to 36% with insulin lispro.

Safety Profile

Moreover, the safety profile of tirzepatide was favourable. The most common adverse events reported were mild to moderate gastrointestinal symptoms, including:

• Nausea (14%-26%)
• Diarrhea (11%-15%)
• Vomiting (5%-13%)

Importantly, hypoglycemia events were significantly lower with tirzepatide, at 0.4 events per patient-year, compared to 4.4 events per patient-year with insulin lispro.

Conclusion

These results are promising for individuals with type 2 diabetes inadequately controlled by basal insulin. Tirzepatide, as an additional therapy to insulin glargine, led to substantial improvements in glycemic control and body weight with a lower risk of hypoglycemia compared to prandial insulin. Such findings offer a potential new treatment avenue that may enhance the management of type 2 diabetes while minimizing some of the challenges associated with traditional insulin therapy. Further research and long-term studies will likely provide more insights into the sustained benefits and safety of tirzepatide in the management of type 2 diabetes.

Reference

Rosenstock, J., Frías, J. P., Rodbard, H. W., Tofé, S., Sears, E., Huh, R., Fernández Landó, L., & Patel, H. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: The SURPASS-6 randomized clinical trial. JAMA: The Journal of the American Medical Association, 2023. https://doi.org/10.1001/jama.2023.20294