At the 58th Annual European Association for the Study of Diabetes (EASD) 2022 meeting in Stockholm, new results were presented from the SURPASS studies regarding Eli Lilly’s recently launched glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide (GLP-1 RA/GIP) dual agonist, tirzepatide (Mounjaro). The data from the SURPASS 1–5 Phase III trials demonstrated that tirzepatide significantly improves postprandial glycemic control in patients with type 2 diabetes (T2D), leading to greater reductions in HbA1c, fasting blood glucose, and body weight versus an active comparator or placebo.
In addition, there was a higher percentage of Time in Range (3.9–10mmol/L) (TIR) observed in a subpopulation of patients in SURPASS-3, with continuous glucose monitoring (CGM) data, on tirzepatide versus insulin degludec. Tirzepatide has demonstrated significant superiority in body weight reduction compared to other GLP-1 RAs, in particular in head-to-head studies with Novo Nordisk’s GLP-1 RA, semaglutide, and has demonstrated significance in achieving glycemic control. Key Opinion Leaders (KOLs) interviewed by GlobalData have expressed their enthusiasm for this therapy and expect significant market uptake and for tirzepatide to become the dominant GLP-1 therapy alongside Novo Nordisk’s semaglutide.
Data for self-monitored blood glucose was collected at baseline and at the primary endpoint for patients randomized across the SURPASS 1–5 trials. The baseline characteristics for the study were: mean age 54.1–63.6 years, duration of T2D 4.7–13.3 years, HbA1c 7.9–8.5%/63.3–69.7mmol/mol, bodyweight 85.9–95.2kg, and body mass index (BMI) 31.9–34.2kg/m2. For groups that had administered tirzepatide versus comparator, the change from baseline in pre-meal to two-hour post-meal excursion daily mean was compared and the proportion of patients achieving a two-hour postprandial self-monitoring blood glucose (SMBG) target goal of less than 10mmol/L and euglycemic less than 7.8mmol/L was also recorded. From the SURPASS-3 CGM substudy of 179 patients, postprandial interstitial glucose (IG) data was identified based on mealtimes recorded during the seven-day period of CGM use, at baseline and Week 52. The proportion of patients who achieved two-hour postprandial IG in TIR (3.9–10mmol/L) and Time in Tight Range (3.9–7.8mmol/L) (TITR) across all meals was calculated.
The study demonstrated that compared to active comparator or placebo, all three doses of tirzepatide led to significant improvement in postprandial glucose excursion. All three doses also led to significantly higher proportion of patients at primary endpoint achieving two-hour postprandial SMBG of less than 10mmol/L (91.9–99.4% tirzepatide versus 61.7–91.2% comparators, p<0.019 for all comparisons except tirzepatide versus semaglutide 1mg in SURPASS-2 [96.3% tirzepatide versus 94.9% semaglutide, p=0.276]), and SMBG less than 7.8mmol/L (64.6–89.7% tirzepatide versus 12.6–62.1% comparator, p≤0.011). For those who completed the CGM in the SURPASS-3 subgroup, all three doses of tirzepatide led to a significantly higher proportion of patients achieving two-hour postprandial IG in TIR (76.3–91.0% tirzepatide versus 63.3% insulin degludec, p<0.017) and TITR (48.6–69.4% tirzepatide versus 35.7% insulin degludec, p=0.041) at Week 52.
Tirzepatide, evidently, leads to significant improvement in postprandial glycemic control with a greater proportion of patients achieving target (<10mmol/L) and euglycemic (<7.8mmol/L) goals compared to placebo or active comparator in patients with T2D. GlobalData predicts that tirzepatide will become the leading GLP-1 agonist in the next decade, significantly challenging the dominant market share that semaglutide has begun to establish.