Table 8: Injectable Agents: GLP-1 RAs GLP-1 RAs
Available Strengths
Starting Dose
How to Titrate Dose
Dosage Range
Generic Name (Trade Name) Semaglutide (Rybelsus) (first oral GLP-1 RA)
• One pill daily with no more than 4 oz of water 30 minutes
• 3 mg once daily.
• Increase to 7 mg once daily for therapeutic dose; may increase to 14 mg once daily as needed for glycemic management.
• 3–14 mg/ daily.
before eating/drinking anything else.
● FLP1-RAs should not be taken at the same time as a DPP-4. ● To decrease side effects, eat smaller meals that are low in fat when taking a GLP-1 RA. ● Risk of weight gain is high if GLP-1 RAs are discontinued.
Key points for patients taking a GLP-1 RA: ● Dose for GLP1 RAs is started low and typically not increased for at least four weeks to reduce nausea and vomiting. ● GLP1 RAs should be discontinued if pancreatitis is suspected. ● There is increased risk of hypoglycemia if given with insulin, sulfonylureas, or meglitinides. In May 2022, the FDA approved tirzepatide (Mounjaro) as the first dual incretin agonist for type 2 diabetes. Tirzepatide is a unique medication in that it combines two classes of drugs: A glucose-dependent insulinotropic polypeptide (GIP) and a GLP-1 RA. Tirzepatide is referred to as a GIP/GLP-1 receptor agonist. Tirzepatide is the first medication in this class and is administered once weekly. This drug demonstrates a significant Mechanism of action Tirzepatide is a synthetic peptide that works to stimulate first- and second-phase insulin secretion. The mechanism of action of the GLP-1 RA component of this drug is described above. Both GLP-1 and GIP hormones promote glucose-stimulated insulin secretion from the pancreatic beta cells, and GIP is the main Side effects Potential side effects are the same as those for the GLP-1 RAs and include nausea, vomiting, diarrhea, decreased appetite, constipation, dyspepsia, and abdominal pain. Taking GLP-1 RAs is a known risk factor for acute pancreatitis. Like GLP-1 RAs, GIP/
GIP/GLP-1 RECEPTOR AGONIST
decrease in A1C and is associated with weight reduction. Aside from tirzepatide (Mounjaro) being approved to improve glycemic control, it has shown promising results for weight loss in people without diabetes. The FDA has recently granted a Fast Track designation to review tirzepatide (Mounjaro) for the treatment of obesity and overweight (Trujillo, 2022).
incretin hormone that exerts insulinotropic effects in response to food intake (Frias, 2020). GIP activity is primarily pancreatic, and GLP-1 activity is primarily systemic (Frias, 2020; Fisman & Tenenbaum, 2021).
GLP-1 RA increases insulin secretion from pancreatic beta cells in a glucose-dependent manner in response to food intake, and thus the risk of hypoglycemia is low. However, when combined with sulfonylureas or insulin, the risk of hypoglycemia increases. ● To decrease side effects, eat smaller meals that are low in fat when taking a GIP/GLP-1 RA. ● To reduce nausea and vomiting, the dose for GIP/GLP-1RA is started low and typically not increased for at least four weeks. ● GIP/GLP RA should be discontinued if pancreatitis is suspected. ● There is increased risk of hypoglycemia if given with insulin, sulfonylureas, or meglitinides. ● The risk of weight gain is high if GIP/GLP-1 RA is discontinued.
Dosing of GIP/GLP-1 RA receptor agonist tirzepatide (Mounjaro) The recommended starting dose is 2.5 mg injected subcutaneously once weekly. After four weeks, increase the dose to 5 mg once weekly. If additional glycemic control is needed, the dose may be increased at a minimum of every four weeks to 7.5 mg once weekly, 10 mg once weekly, 12.5 mg once weekly, and a maximum dose of 15 mg once weekly. Key points for patients taking a GIP/GLP-1 RA: ● A GIP/GLP-1 RA should not be taken at the same time as a DPP-4.
Evidence-Based Practice There is evidence that the efficacy of tirzepatide (Mounjaro), a unique combination of GLP-1RA and GIP, has weight loss effects that are superior to semaglutide (Ozempic), with promising effects for people with and without diabetes. A randomized control trial (RCT) was conducted at 119 sites in nine countries. Adults over the age of 18 with a body mass index (BMI) of 30 or more, with one or more unsuccessful dietary efforts to lose weight, were recruited and invited to participate in the study. Subjects were randomly assigned to receive a dose of 5 mg, 10 mg, or 15 mg once weekly for 72 weeks as an adjunct to lifestyle intervention. The most common side effect with use of tirzepatide was gastrointestinal disturbances, with most being mild to moderate in severity and occurring mostly during dose escalation. Results indicated that all three doses of once weekly tirzepatide demonstrated substantial and sustained weight reduction in adults with obesity. Improvements in other cardiometabolic measures were likewise observed (Jastreboff et al., 2022).
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