ADA: Eli Lilly’s next-gen GLP-1 moves the needle in early-stage diabetes ahead of FDA filing

Chalk another one up for Eli Lilly’s next-generation diabetes drug. All three doses of tirzepatide beat placebo at lowering blood sugar and body weight in adults with early-stage Type 2 diabetes, more than half of whom had never tried a diabetes-specific treatment.  

Tirzepatide combines two mechanisms into one drug: It dials up GIP in addition to GLP-1, the target of well-known diabetes meds like Novo Nordisk’s semaglutide, sold as Ozempic and Rybelsus, and Lilly's own dulaglutide, sold as Trulicity. Lilly figured that combining the two could be even more effective, and signs are pointing to yes. 

After 40 weeks of treatment, patients taking the highest dose, 15 mg, lost an average of 11% of their body weight and saw their blood sugar drop by 2.07%, as gauged by A1C, a measure of average blood glucose over two to three months. More than half of the patients taking the highest dose saw their blood sugar fall below 5.7%, a level considered normal. 

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The top dose fared the best, but the two lower doses, 5 mg and 10 mg, also beat placebo on those measures. All three doses also improved patients’ fasting blood sugar levels, as well as their blood sugar levels taken two hours after a meal in the phase 3 study, dubbed Surpass-1. 

These figures repressent results in patients who took the drug to the letter: “They have taken the drug and have stayed on the drug; they have not discontinued it, and they have not started any other glucose lowering agent, like rescue therapies due to poor glycemic control,” said Laura Fernández Landó, Eli Lilly’s senior medical director for the tirzepatide development program in Type 2 diabetes. 

The company also reported another set of figures that cover patients who've received at least one dose of tirzepatide and stayed in the study, irrespective of whether they stuck to taking the drug, or whether they took a rescue therapy or not, Fernández Landó said. 

RELATED: Lilly's tirzepatide aces 5th phase 3, teeing up approval filings 

These figures are, understandably, somewhat lower—patients taking the top dose saw a 1.69% reduction in blood sugar compared to the 2.07% seen in the more conscientious group—but are what regulators want to see as they are closer to how the drug is expected to perform in the real world. 

The drug’s safety profile was similar to that of other GLP-1 drugs. The most common side effects were gastrointestinal and were mostly mild to moderate, including nausea, diarrhea and vomiting. 

Less than 10% of the patients taking the two lower doses of tirzepatide quit the study, while this figure was higher for those taking the top dose (22%) and placebo (15%). However, most of the patients in the 15 mg and placebo groups who left did so for “reasons other than adverse events,” including concerns about the pandemic, family or work. 

The data, published in The Lancet and presented virtually on Saturday at the annual meeting of the American Diabetes Association, come from one of five phase 3 studies that will support an FDA submission for tirzepatide by the end of the year. 

RELATED: Lilly's tirzepatide beats Novo's semaglutide in diabetes phase 3, but another study muddies picture 

The company also presented data from three of those studies at the meeting. One trial pitted tirzepatide against Novo Nordisk’s Tresiba (insulin degludec); another compared it to placebo as an add-on treatment to insulin glargine, marketed by Sanofi as Lantus and Toujeo; and the last tested it against Novo Nordisk’s Ozempic. In all three, tirzepatide outshone its contenders. 

“In the Surpass program, we have studied tirzepatide across the whole diabetes treatment spectrum, from monotherapy in patients with a short duration of diabetes to patients who have 13 years duration of diabetes and... require an additional therapy beyond basal insulin,” Fernández Landó said.