The medical community has made significant advancements in developing treatments for metabolic conditions such as obesity and type 2 diabetes. These new medications are transforming how these widespread health challenges are managed. They offer novel approaches to improving metabolic health and achieving substantial weight loss. The emergence of these therapies represents a notable shift in the therapeutic landscape.
Understanding Their Mechanisms
The scientific basis for these medications involves targeting incretin hormones, which are naturally released by the gut in response to food intake. Two primary incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). These hormones play a role in regulating blood sugar levels and appetite.
Tirzepatide acts as a dual agonist, activating both GIP and GLP-1 receptors. Activating GIP receptors enhances insulin secretion in a glucose-dependent manner and may also improve fat metabolism and energy expenditure. Activating GLP-1 receptors stimulates insulin release, suppresses glucagon secretion (which lowers hepatic glucose production), slows gastric emptying, and promotes satiety, leading to reduced food intake. This dual engagement provides a synergistic effect, enhancing glucose control and promoting weight loss.
Survodutide functions as a dual agonist for GLP-1 and glucagon receptors. GLP-1 receptor activation contributes to appetite suppression, delayed gastric emptying, and glucose-dependent insulin secretion. Glucagon receptors (GCGR) are thought to increase energy expenditure and influence fat burning. This dual action aims to achieve weight loss and metabolic improvements by combining appetite suppression with increased energy use.
Primary Therapeutic Applications
Tirzepatide has received regulatory approvals for two conditions. It is approved under the brand name Mounjaro for improving glycemic control in adults with type 2 diabetes mellitus (May 2022). In November 2023, it was also approved for chronic weight management in adults with obesity or those who are overweight with at least one weight-related condition, marketed as Zepbound.
Survodutide is primarily under investigation for chronic weight management and metabolic dysfunction-associated steatohepatitis (MASH). MASH is a progressive liver disease characterized by fat accumulation, inflammation, and potential scarring. Survodutide is currently undergoing Phase III trials for obesity and overweight, including studies in individuals with and without type 2 diabetes, cardiovascular disease, and chronic kidney disease.
Effectiveness in Clinical Trials
Clinical trials have provided data on the effectiveness of both medications. In the SURMOUNT-1 trial, involving adults with obesity or overweight without type 2 diabetes, tirzepatide (15 mg) led to an average body weight reduction of 22.9% after 176 weeks. Participants in the SURMOUNT-2 study, with type 2 diabetes and obesity, experienced an average weight loss of 15% over 72 weeks, alongside an HbA1c reduction from 8% to 5.9%. Across the SURPASS-1 to -5 trials, tirzepatide demonstrated significant HbA1c reductions (1.87% to 3.02%) and body weight reductions (5.4 to 12.9 kg) over treatment periods up to 104 weeks.
Survodutide has shown promising results. In a Phase II dose-finding study for individuals with overweight or obesity, survodutide led to a mean body weight loss of up to 18.7% after 46 weeks with the 4.8 mg dose. In a separate Phase II trial involving patients with type 2 diabetes, survodutide achieved a mean HbA1c reduction similar to semaglutide and showed greater body weight reductions, up to 8.7% compared to 5.3% with semaglutide after 16 weeks.
Side Effects and Administration
Both tirzepatide and survodutide are administered as once-weekly subcutaneous injections. For tirzepatide, dosage is typically increased over four to 20 weeks to reach maintenance doses of 5 mg, 10 mg, or 15 mg. Survodutide’s Phase III trials involve maintenance doses of 3.6 mg or 6.0 mg.
Common side effects for both medications are largely gastrointestinal, including nausea, vomiting, diarrhea, and constipation. Tirzepatide can also cause stomach pain, burping, heartburn, and flatulence. Survodutide also reports dyspepsia. These effects are often mild to moderate and tend to occur more frequently during initial dose escalation. More serious, though rare, side effects for tirzepatide include gallbladder disease, pancreatitis, and acute kidney injury due to dehydration.
Key Distinctions and Patient Considerations
The primary distinction between survodutide and tirzepatide lies in their specific receptor targets. Tirzepatide activates both GLP-1 and GIP receptors, influencing glucose regulation and appetite. Survodutide targets GLP-1 and glucagon receptors, combining appetite suppression with increased energy expenditure and direct liver effects. This difference in receptor engagement may lead to varied metabolic responses and side effect profiles.
When considering these treatments, patients and healthcare providers should evaluate several factors. Specific health goals are important, such as whether the primary focus is on weight loss, diabetes management, or addressing conditions like MASH. Individual response and tolerability to side effects, particularly gastrointestinal issues, also play a role. Ultimately, treatment decisions should always be made in close consultation with a healthcare professional to align with individual health needs.