Eli Lilly and Company's announced phase 3 SURPASS-3 clinical trial. The CGM sub-study was presented at the 57thEuropean Association for the Study of Diabetes (EASD) Annual Meeting in an EASD-sponsored symposium. 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. 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% 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). The SURPASS-3 sub-studies and the SURPASS clinical trial program: Lilly developed two sub-studies in order to assess additional glycemic control measures and the effect on liver fat content and abdominal adipose tissue in SURPASS-3, a 52-week randomized, phase 3, open-label trial evaluating the efficacy and safety of tirzepatide compared to titrated insulin degludec in adults with type 2 diabetes who have inadequate glycemic control on stable doses of metformin with or without an SGLT-2 inhibitor. In SURPASS-3, 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. 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. Diabetes: An estimated 463 million adults worldwide have diabetes. Type 2 diabetes is the most common type, accounting for an estimated 90% to 95% of all diabetes cases. Diabetes is a chronic disease that occurs when the body does not properly produce or use the hormone insulin.