Medications for weight loss should be combined with physical activity including resistance training. Incretin medications will reduce appetite / increase satiety leading to reduced intake of food. Healthy eating choices are essential to overall health.
For more information on physical activity click here and on healthy diet click here. For more information on weight loss options click here. To go to the main Health Matters website click here.
Incretin Based Medications for Diabetes and Weight Management
“Incretin based medications'' include 3 classes of medications based on mechanism of action: a) GLP-1 receptor agonist; b) Dual-acting GLP-1 agonist and GIP agonist; c) Dipeptidyl peptidase 4 (DPP-4) inhibitors. DPP-4 inhibitors are not as effective and will not be presented here. All of the medications in the 2 main classes of incretin based medications lower blood sugars and have the potential to aid in weight loss. However only Tirzepatide (Zepbound), Liraglutide (Saxenda) and Semaglutide (Wegovy) are FDA approved for weight management. It is my opinion that when used for weight management medications should be combined with exercise including resistance training to help maintain muscle and bone health.
Below is a listing of all of the medications (and doses) in these classes that are available as of July 20, 2024. Following the listing is information from the authors of the professional resource uptodate.com.
GLP-1 receptor agonist
Semaglutide (Ozempic, Wegovy ) (weekly)
Ozempic and Wegovy are brand names for semaglutide. Ozempic is FDA approved for diabetes. Wegovy is FDA approved for weight management. There are different dosing schedules for these medications depending on if they are primarily used for weight management or diabetes.
Weight management, chronic (Wegovy) (weekly injection):
Wegovy is injected subcutaneously in the abdomen, thigh, or upper arm once weekly. The initial dose is 0.25 mg once weekly for four weeks. The dose is increased at four-week intervals (0.5, 1, 1.7, 2.4 mg) to the recommended dose of 1.7 or 2.4 mg once weekly.
Diabetes mellitus, type 2, treatment (Ozempic, Rybelsus):
Oral (Rybelsus): 3 mg once daily for 30 days, then increase to 7 mg once daily; may increase to 14 mg once daily after 30 days on the 7 mg dose if needed to achieve glycemic goals. Note: The lower initial dose (3 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control. A study has shown that 50 mg daily of oral semaglutide was effective for weight loss as injectable but this dose has not been FDA approved. Oral semaglutide at standard dose may not be as effective for prevention of cardiac problems as injectable semaglutide.
Subcutaneous injection (Ozempic): Initial: 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg once weekly. May increase to 1 mg once weekly after 4 weeks on the 0.5 mg/week dose if needed to achieve glycemic goals; may increase further to 2 mg once weekly after 4 weeks on the 1 mg/week dose if needed to achieve glycemic goals (maximum: 2 mg/week).
GLP-1 receptor agonist
(continued)
Dulaglutide (Trulicity) (weekly) (FDA approved for diabetes)
Subcutaneous injection Initial: 0.75 mg once weekly; may increase to 1.5 mg once weekly after 4 to 8 weeks if needed.
Exenatide extended release (Bydureon BCise) (weekly injection) (FDA approved for diabetes)
Subcutaneous injection 2 mg once weekly
Exenatide (Byetta) (twice daily) (FDA approved for diabetes)
Initial: 5 mcg twice daily may increase to 10 mcg twice daily after 1 month
Liraglutide (Victoza, Saxenda) (daily)
Victoza and Saxenda are brand names for liraglutide. Victoza is FDA approved for diabetes. Saxenda is FDA approved for weight management. There are different dosing schedules for these medications depending on if they are primarily used for weight management or diabetes.
Weight management, chronic (Saxenda) (weekly injection) :
Initial: 0.6 mg once daily for 1 week; increase by 0.6 mg daily at weekly intervals to a target dose of 3 mg once daily.
Diabetes mellitus, type 2, treatment (Victoza) (weekly injection):
Initial: 0.6 mg once daily for 1 week, then increase to 1.2 mg once daily; if optimal glycemic response is not achieved after an additional week of treatment, may increase further to 1.8 mg once daily. Note: The lower initial dose (0.6 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control.
Lixisenatide (Adlyxin) (daily injection)
Initial: 10 mcg once daily for 14 days; on day 15 increase to 20 mcg once daily. Maintenance dose: 20 mcg once daily.
Dual-acting GLP-1 agonist and GIP agonist
(tirzepatide only currently approved medication in this class)
Tirzepatide (Mounjaro) (Zepbound)
Tirzepatide is administered by once-weekly subcutaneous injection. The starting dose is 2.5 mg once weekly for four weeks and then increased to 5 mg once weekly. The dose may be increased in 2.5 mg increments at a minimum of four-week intervals to the maximum dose of 15 mg once weekly. Dosing of tirzepatide for diabetes and weight management are the same. Mounjaro is the brand name that is FDA approved for diabetes; Zepbound is the brand name FDA approved for weight management- they are the same drug just different names for the 2 FDA indications.
Discussion
The below text is adapted from uptodate.com (7-22-2024).
For individuals with overweight or obesity in whom pharmacologic therapy is indicated, we (authors of uptodate.com article) suggest tirzepatide or semaglutide rather than other agents (Grade 2C). Indirect comparisons suggest that they may have superior efficacy for weight loss.
The selection between tirzepatide and semaglutide depends on patient preferences and comorbidities. Tirzepatide likely results in greater weight loss, but semaglutide has demonstrated reductions in major cardiovascular events in individuals both with and without diabetes. Liraglutide and dulaglutide (for those with diabetes) are acceptable but less efficacious alternatives. However, they also have likely cardiovascular and kidney benefits in the subset of patients with diabetes and with or at high risk of cardiovascular disease.
Two randomized trials in adults with obesity demonstrated mean losses of 15 to 21 percent body weight with the highest dose of tirzepatide (15 mg weekly, trials were 72 weeks). In the larger of the two trials, over 80 percent of participants in all tirzepatide treatment groups (5 to 15 mg weekly) lost ≥5 percent of body weight, compared with 35 percent of those assigned to placebo. Dose-related gastrointestinal side effects (nausea, diarrhea, constipation) were common but generally mild. Although direct comparisons are limited, the magnitude of weight loss with tirzepatide appears greater than that with other agents; thus, we consider tirzepatide a preferred medication for chronic weight management.
Effects of tirzepatide discontinuation on weight (February 2024): Among adults with obesity who had previously lost weight (21 percent mean weight reduction) during a 36-week, open-label trial of tirzepatide, those randomly assigned to continue tirzepatide for 52 weeks experienced additional weight loss, whereas those assigned to placebo partially regained (-5.5 versus +14 percent mean weight change, respectively). These results, in line with those of previous studies, suggest that most individuals with obesity who opt for pharmacotherapy will require long-term treatment for weight loss maintenance.
In uptodate.com section on treatment of diabetes:
Choice of therapy — When a decision has been made to use GLP-1 receptor agonist-based therapies, our selection of a particular agent is guided by the presence of underlying patient comorbidities, in particular ASCVD, as well as by glycemic efficacy.
(ASCVD = Atherosclerotic cardiovascular disease)
●With clinical ASCVD – In patients with clinical ASCVD (eg, prior myocardial infarction, stroke), we suggest liraglutide, semaglutide (subcutaneous), or dulaglutide, based on the respective cardiovascular outcomes study results. (See 'Cardiovascular effects' below.)
The progression of retinopathy seen in the subcutaneous semaglutide study is likely a consequence of rapid glycemic lowering (similar to that seen in other settings) rather than a direct effect of the drug (see 'Microvascular outcomes' below). If subcutaneous semaglutide is prescribed to a patient with a history of diabetic retinopathy, consideration should be given to slower titration to avoid rapid declines in A1C and retinal screening within six months of drug initiation to detect progression of retinopathy. The caution regarding rapid lowering of glycemia and risk of retinopathy applies to all glucose-lowering medications.
●Without ASCVD – In patients without ASCVD, we prefer long- over short-acting GLP-1-based therapies due to patient convenience and greater glycemic efficacy. For patients in whom weight loss is a primary consideration, subcutaneous semaglutide or tirzepatide is preferred . Among the longer-acting agents (liraglutide, exenatide once weekly, dulaglutide, subcutaneous semaglutide, tirzepatide), the need for reconstitution (subcutaneous preparations), patient preference, and payer coverage are also important considerations.
No comparative trials have evaluated the effects of different GLP-1-based therapies on patient-important, long-term outcomes such as microvascular complications, health-related quality of life, or mortality. A number of comparative trials have included glycemia as the primary outcome, and some have included weight loss as a secondary outcome.
●Shorter acting versus longer acting – In trials comparing exenatide administered twice daily with exenatide once weekly, liraglutide once daily, or dulaglutide once weekly, the reduction in A1C with the longer-acting (daily or weekly) GLP-1 receptor agonists was significantly greater (treatment difference -0.3 to -0.7 percent).
●Longer acting – Among the longer-acting GLP-1-based therapies, small differences in glycemic efficacy favor tirzepatide over subcutaneous semaglutide (1 mg), liraglutide or subcutaneous semaglutide over exenatide once weekly, and subcutaneous semaglutide over dulaglutide or liraglutide. Glycemic management appears to be similar with liraglutide and dulaglutide and with oral semaglutide and liraglutide [36]. (See 'Glycemic efficacy' below.)
In these trials, weight loss was generally better with subcutaneous semaglutide (-6 kg) than once-weekly exenatide (-2 kg), dulaglutide (-3 kg), and 1.2 mg liraglutide (-2 kg), as well as with 1.8 mg liraglutide (-3.5 kg) compared with once-weekly exenatide (-2.5 kg) and dulaglutide (-3 kg). Tirzepatide resulted in greater weight loss than subcutaneous semaglutide (1 mg).
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