Lilly's tirzepatide led to greater time in range compared to insulin degludec in adults with type 2 diabetes in SURPASS-3 CGM sub-study
The international consensus for time in range recommends a target of >70% time in range (70-180 mg/dL) for most people with diabetes as well as a target of <4% time below range 70 mg/dL and <25% time above range 180 mg/dL.2 In an exploratory endpoint of this CGM sub-study, participants taking tirzepatide 15 mg experienced 91.2% time in range (71-180 mg/dL) at 52 weeks.
"The CGM data collected through this SURPASS-3 sub-study show that tirzepatide helped participants have less variability in their blood glucose levels throughout the day, including spending less time below target range and more time in a tighter target range reflecting a normal blood glucose range," said
Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes.
SURPASS-3 was a 52-week, multi-center, randomized, phase 3, open-label trial evaluating the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg compared to titrated insulin degludeci in adults with type 2 diabetes who have inadequate glycemic control on stable doses of metformin with or without an SGLT-2 inhibitor. Study participants were insulin-naïve and had a mean duration of diabetes of 8.4 years, a baseline A1C of 8.17 percent and a baseline weight of 94.3 kg.
In the SURPASS-3 CGM sub-study, a subpopulation of 243 participants wore a CGM for 7 to 10 days at baseline, at 24 weeks and at 52 weeks to evaluate the effect of tirzepatide compared to insulin degludec on time in the hyper- and hypoglycemic range and on glycemic variability. Glycemic variability was measured during 24-hour periods by several measures, including the coefficient of variation (CV).
The CGM sub-study achieved its primary and secondary endpoints. Specifically, at 52 weeks, the primary endpoint showed that participants taking tirzepatide:
- Spent 72.6% of the 24-hour period in tight target range (71-140 mg/dL) for pooled 10 mg and 15 mg arms, an average of approximately six more hours than those taking insulin degludec (48.0%).
Additional exploratory endpoints showed that at 52 weeks, participants taking tirzepatide:
- Spent between 84.9% and 91.2% of the 24-hour period in the target time in range (71-180 mg/dL), compared to 75% for those taking insulin degludec.
- Spent less time in hypoglycemia across all three doses compared to insulin degludec. Time spent ≤70 mg/dL was between 0.6% and 1.0% for tirzepatide and 2.4% for insulin degludec. Time spent <54 mg/dL was between 0.11% and 0.14% for tirzepatide and 0.39% for insulin degludec.
- Experienced a significant reduction in the coefficient of variation (CV) during a 24-hour period (between 0.9-3.4%) compared to an increase in CV for those taking insulin degludec.
The overall safety profile of tirzepatide in SURPASS-3 was similar to the well-established GLP-1 receptor agonist class. Gastrointestinal side effects were the most commonly reported adverse events and decreased with continued dosing.
Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose and body weight. Tirzepatide is in phase 3 development for blood glucose management in adults with type 2 diabetes and for chronic weight management. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction (HFpEF).
About the SURPASS-3 sub-studies and the SURPASS clinical trial program
The SURPASS-3 CGM sub-study compared the effect of tirzepatide to titrated insulin degludec evaluated by continuous glucose monitoring (CGM) in a subpopulation of participants with type 2 diabetes from the SURPASS-3 trial. In the sub-study, 243 participants wore a CGM for seven to ten days at baseline, at 24 weeks and at 52 weeks and were randomized to receive either tirzepatide 5 mg, 10 mg or 15 mg or titrated insulin degludec. The primary objective of the sub-study was to demonstrate superiority of tirzepatide (pooled 10 mg and 15 mg) once-weekly compared to insulin degludec for the percentage of time in tight target range (71-140 mg/dL) at 52 weeks. Key secondary endpoints included comparing tirzepatide 5 mg, 10 mg and 15 mg versus insulin degludec for the percentage of time per day spent in tight target range (71-140 mg/dL) and for the duration of time (in minutes) per day spent in tight target range (71-140 mg/dL). Exploratory endpoints include time spent in target range (71-180 mg/dL), time spent below target range (≤70 mg/dL and <54 mg/dL) and change in the coefficient of variation.
The SURPASS phase 3 global clinical development program for tirzepatide has enrolled more than 20,000 people with type 2 diabetes across 10 clinical trials, five of which are global registration studies. The program began in late 2018, and all five global registration trials have been completed.
An estimated 463 million adults worldwide3 have diabetes. Type 2 diabetes is the most common type, accounting for an estimated 90 to 95 percent of all diabetes cases4. Diabetes is a chronic disease that occurs when the body does not properly produce or use the hormone insulin.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about tirzepatide as a potential treatment for people with type 2 diabetes and the timeline for future readouts, presentations and other milestones relating to tirzepatide and its clinical trials and reflects
1 Battelino, T. Effect of tirzepatide on glycaemic control captured with continuous glucose monitoring in patients with type 2 diabetes (SURPASS-3 CGM). Session S42a. Presented virtually at the 57th
2 Battelino T, Danne T, Bergenstal RM, et al. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019;42(8):1593-1603.
3 International Diabetes Federation. IDF Diabetes Atlas, 9th edn.
4 Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020.
i The mean starting dose of insulin degludec was 10 units per day. The insulin dose was titrated following a treat-to-target algorithm with the goal of fasting blood glucose below 90 mg/dL.
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