Tirzepatide, the active ingredient in Zepbound and Mounjaro, has demonstrated a significant reduction in the risk of developing type 2 diabetes among adults with pre-diabetes and obesity or overweight. A phase 3 clinical trial revealed a 94% risk reduction compared to placebo, alongside substantial and sustained weight loss. These findings, coupled with a meta-analysis indicating tirzepatide's superiority over insulin in managing type 2 diabetes, suggest a potential paradigm shift in diabetes prevention and treatment.
Tirzepatide's Impact on Diabetes Risk and Weight Management
The SURMOUNT-1 study, a three-year trial involving 1,032 participants, evaluated the efficacy and safety of weekly tirzepatide injections (5 mg, 10 mg, 15 mg) compared to placebo. The results showed a remarkable 94% reduction in the risk of progressing to type 2 diabetes among adults with pre-diabetes and obesity or overweight. Furthermore, participants on the 15 mg dose experienced an average weight loss of 22.9% compared to a 2.1% reduction in the placebo group.
Jeff Emmick, senior vice president at Eli Lilly, emphasized the significance of these findings, stating, "Tirzepatide reduced the risk of developing type 2 diabetes by 94% and resulted in sustained weight loss over the three-year treatment period. These data reinforce the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes."
However, during a 17-week off-treatment follow-up period, participants who discontinued tirzepatide began to regain weight and showed some increase in the progression to type 2 diabetes, resulting in an 88% reduction in the risk of progression to type 2 diabetes compared to placebo.
Tirzepatide vs. Insulin: A Meta-Analysis
A recent meta-analysis published in the International Journal of Obesity compared the safety and efficacy of once-weekly tirzepatide against conventional long- and ultra-long-acting insulin supplements in managing type 2 diabetes. The analysis, encompassing data from the SURPASS-3, SURPASS-4, and SURPASS-AP-Combo randomized clinical trials with 4,339 patients, revealed that tirzepatide matched or outperformed insulin in both safety and efficacy.
The study found that tirzepatide led to a significant weight reduction of 10.61 kg, a decrease in systolic and diastolic blood pressure by 6.47 mmHg and 2.3 mmHg, respectively, and improved lipid profiles, including reductions in triglycerides (14.49%) and cholesterol (total—4.78%, LDL—5.98%, and VLDL—14.18%).
The meta-analysis also highlighted that tirzepatide achieved near-normal HbA1c readings in a shorter time frame compared to insulin supplements (8.1 weeks versus 12.1 weeks). While higher doses of tirzepatide were associated with a slightly increased risk of hypoglycemia and nausea, these side effects were comparable to or lower than those observed with equivalent insulin dosages.
Mechanism of Action and Clinical Implications
Tirzepatide is a dual agonist with characteristics of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It works by activating these two hormone receptors, improving blood sugar control and suppressing appetite. This dual action contributes to its effectiveness in both weight management and diabetes prevention.
The findings from the SURMOUNT-1 study and the meta-analysis suggest that tirzepatide could potentially replace insulin treatment as an improved clinical intervention for patients with type 2 diabetes. Its ability to reduce diabetes risk, promote sustained weight loss, and improve cardiovascular and metabolic parameters positions it as a valuable tool in addressing the growing global burden of diabetes and obesity.
Detailed results from the SURMOUNT-1 study will be submitted to a peer-reviewed journal and presented at ObesityWeek 2024 in November.
