Lilly's SURPASS-1 results published in The Lancet show tirzepatide's superior A1C and body weight reductions versus placebo in adults with type 2 diabetes.

Detailed SURPASS-1 results were presented in an oral presentation during the American Diabetes Association's (ADA) 81st Scientific Sessions, were simultaneously published in The Lancet and will be featured during an ADA-sponsored symposium on Tuesday, June 29.

Study participants in SURPASS-1, 54.2 percent of whom were treatment-naïve, had a relatively short mean duration of diabetes of 4.7 years, a baseline A1C of 7.9 percent and a baseline weight of 85.9 kg. For the efficacy estimand, tirzepatide reduced A1C by up to 2.07 percent and body weight by up to 9.5 kg (20.9 lb., 11.0 percent) compared to placebo (+0.04 A1C change and body weight change of -0.7 kg [1.5 lb., 0.9 percent]). Up to 52 percent of participants achieved an A1C less than 5.7 percent – the level seen in people without diabetes. Tirzepatide also led to improvements in the change in fasting serum glucose from baseline. In an additional secondary endpoint, tirzepatide led to improvements in the change in two-hour post-meal glucose values from baseline from self-monitored blood glucose data.

The overall safety profile of tirzepatide was similar to the well-established glucagon-like peptide-1 (GLP-1) receptor agonist class, with gastrointestinal side effects being the most commonly reported adverse events. Treatment discontinuation rates due to adverse events were less than 7 percent in each tirzepatide treatment arm.

For both estimands all three tirzepatide doses reached statistical significance in A1C and body weight reductions from baseline and in the percentage of participants who achieved an A1C of less than 7 percent (the American Diabetes Association's recommended target for people with diabetes) or less than 5.7 percent. At 40 weeks, tirzepatide led to a significant decrease in fasting serum glucose (FSG) compared to placebo. In an additional secondary endpoint, the mean two-hour post-meal glucose values for tirzepatide across all three doses were under 140 mg/dL (considered normal values in individuals without diabetes).

Specifically, the efficacy estimand results showed : i.A1C change: -1.87% (5 mg), -1.89% (10 mg), -2.07% (15 mg), +0.04% (placebo). ii. Weight reduction: -7.0 kg (-7.9%, 5 mg), -7.8 kg (-9.3%, 10 mg), -9.5 kg (-11.0%, 15 mg), -0.7 kg (-0.9%, placebo). iii. Percent of participants achieving A1C <7%: 87% (5 mg), 92% (10 mg), 88% (15 mg), 20% (placebo). iv. percent of participants achieving a1c><5.7%: 34% (5 mg), 31% (10 mg), 52% (15 mg), 1% (placebo) v. change in fsg: -43.6 mg dl (5 mg), -45.9 mg dl (10 mg), -49.3 mg dl (15 mg), +12.9 mg dl (placebo).></5.7%:></7%:>

The treatment-regimen estimand results showed : i. A1C reduction: -1.75% (5 mg), -1.71% (10 mg), -1.69% (15 mg), -0.09% (placebo). ii. Weight reduction: -6.3 kg (5 mg), -7.0 kg (10 mg), -7.8 kg (15 mg), -1.0 kg (placebo) iii. Percent of participants achieving A1C <7%: 82% (5 mg), 85% (10 mg), 78% (15 mg), 23% (placebo). iv. percent of participants achieving a1c><5.7%: 31% (5 mg), 27% (10 mg), 38% (15 mg), 1% (placebo). v. change in fsg: -39.6 mg dl (5 mg), -39.8 mg dl (10 mg), -38.6 mg dl (15 mg), +3.7 mg dl (placebo.></5.7%:></7%:>

No events of severe hypoglycemia or hypoglycemia less than 54 mg/dL were observed in the tirzepatide treatment arms . In an additional exploratory endpoint, all three doses of tirzepatide led to favorable changes from baseline in fasting lipids. Specifically, at the highest dose of tirzepatide (15 mg): total cholesterol was reduced by 8.4 percent, triglycerides were reduced by 21.0 percent, low-density lipoprotein (LDL) cholesterol was reduced by 12.4 percent, very low-density lipoprotein (VLDL) cholesterol was reduced by 19.8 percent, and high-density lipoprotein (HDL) cholesterol was increased by 7.5 percent.

The most commonly reported adverse events for tirzepatide were gastrointestinal-related and mostly mild to moderate in severity, usually occurring during the dose escalation period. For study participants treated with tirzepatide (5 mg, 10 mg and 15 mg, respectively), nausea (11.6 percent, 13.2 percent, 18.2 percent, respectively), diarrhea (11.6 percent, 14.0 percent, 11.6 percent, respectively), vomiting (3.3 percent, 2.5 percent, 5.8 percent, respectively) and constipation (5.8 percent, 5.0 percent, 6.6 percent, respectively) were more frequently experienced compared to placebo (6.1 percent [nausea], 7.8 percent [diarrhea], 1.7 percent [vomiting], 0.9 percent [constipation]). The overall treatment discontinuation rates were 9.1 percent (tirzepatide 5 mg), 9.9 percent (tirzepatide 10 mg) and 21.5 percent (tirzepatide 15 mg), compared to 14.8 percent (placebo). The majority of the discontinuations in the 15 mg and placebo arms were due to reasons other than adverse events (such as concerns due to the coronavirus pandemic and family or work reasons).

SURPASS-1 is the first of five global registration studies for tirzepatide in type 2 diabetes, all of which have been completed. Lilly intends to submit the full registration package to regulatory authorities by the end of 2021.

See- " Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial".- Julio Rosenstock, MD, Carol Wysham, MD, Juan P Frías, MD, et al. Published:June 26, 2021DOI:https://doi.org/10.1016/S0140-6736(21)01324-6. The Lancet.