Recent headlines have been abuzz with the groundbreaking weight loss results achieved with the injectable drug semaglutide, demonstrating the potential for people with obesity to shed up to 20 percent of their body weight. These findings have sparked considerable interest, particularly given that conventional lifestyle interventions typically yield only 5 to 10 percent weight loss. Eli Lilly is poised to take this innovation further with two potential injectable medications — tirzepatide and retatrutide — currently awaiting approval for the treatment of obesity and type 2 diabetes.
Mimicking Multiple Hormones for Enhanced Efficacy
The new medications work by mimicking multiple hormones involved in regulating appetite and blood sugar. In addition to being a glucagon-like peptide 1 (GLP-1) receptor agonist, like semaglutide, tirzepatide also mimics glucose-dependent insulinotropic polypeptide (GIP), a hormone involved in blood glucose regulation and the storage of excess energy in fat cells.
One study compared tirzepatide in three different weekly doses (5mg, 10mg, and 15mg) with the standard weekly 1mg semaglutide injection. All three doses of tirzepatide led to more substantial weight loss than the 1mg semaglutide injection. Research also suggests that the higher doses (10mg and 15 mg) of tirzepatide may outperform a 2mg semaglutide dose, resulting in more weight loss (3.15 kg and 5.15kg, respectively).
Two Phase III clinical trials, SURMOUNT-3 and SURMOUNT-4, evaluated tirzepatide compared to a placebo in people with obesity or weight-related comorbidities. For SURMOUNT-3, all participants first received a 12-week intervention that included a low-calorie diet, exercise, and weekly counseling. The average weight loss during this period was 6.9 percent. Following this intervention, participants were randomized to receive either tirzepatide or a placebo. After the 72-week treatment phase, those receiving tirzepatide lost, on average, an additional 21.1 percent of their body weight, while those in the placebo group regained, on average, 3.3. percent body weight.
All participants in SURMONT-4 took tirzepatide for the first 36 weeks, with an average weight loss of 21.1 percent. This was followed by randomization and a 52-week study period. Participants in the treatment group had an average 25.3 percent body weight loss over the 88-week trial, compared to an average weight regain of 14 percent among the placebo group. “The findings from SURMOUNT-3 challenge the notion that patients living with obesity or overweight can achieve their weight loss goals with diet and exercise alone, said Jeff Emmick, senior vice president, product development at Eli Lilly, in a statement. “The findings from SURMOUNT-4 reinforce that obesity should be regarded like other chronic diseases where chronic therapy may be needed to maintain treatment benefits,” he added.
Retatrutide: A Triple-Hormone Receptor Agonist
Retatrutide is a triple-hormone receptor agonist that mimics GLP-1, GIP, and glucagon. In the brain, GLP-1 reduces appetite and food-seeking behaviors. In the gut and pancreas, it helps to control blood sugar levels. GIP also regulates blood sugar and affects fat cells’ energy absorption. Glucagon plays a role in preventing low blood sugar levels during fasting, exercise, or low-carb intake. A randomized clinical trial of retatrutide showed that participants, who received either 1 mg, 4 mg, 8mg, or 12 mg doses per week, achieved substantial weight loss after 48 weeks of treatment. All participants who received at least 4 mg weekly doses lost at least 5 percent of their body weight. Those who received the highest dose achieved a mean weight reduction of 24.2 percent, translating to an average absolute weight reduction of about 58 pounds over 11 months of the study, the company reported in a statement.
The Future of Weight Loss Medications
The weight loss medication landscape is changing rapidly, as researchers continue to explore new compounds to regulate appetite and blood sugar while enhancing the efficacy and safety of these drugs. Following the attention received by semaglutide, potential options like tirzepatide and retatrutide loom on the horizon, offering hope for additional weight loss solutions in the future.
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