From the Guidelines
If someone does not achieve adequate weight loss with Glucagon-like peptide (GLP) receptor agonists, trying a dual Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, such as tirzepatide, is a reasonable next step. According to the most recent guidelines from the Diabetes Care journal 1, prioritizing medications with a beneficial effect on weight is crucial for achieving both glycemic and weight management goals in diabetes treatment. The guidelines suggest that a dual GIP and GLP-1 receptor agonist, such as tirzepatide, may be considered for people with type 2 diabetes and overweight or obesity who do not achieve adequate weight loss with GLP-1 receptor agonists alone 1.
Some key points to consider when using dual GIP and GLP-1 receptor agonists include:
- Starting with a low dose and gradually increasing to a target dose to minimize side effects 1
- Monitoring for potential side effects, such as nausea, vomiting, and diarrhea 1
- Considering the potential benefits of dual GIP and GLP-1 receptor agonists, including greater weight loss efficacy and added weight-independent benefits, such as glycemic and cardiometabolic benefits 1
- Evaluating the need for continued treatment beyond reaching weight loss goals to maintain health benefits 1
It's essential to note that the guidelines recommend reevaluating weight management therapies and intensifying treatment with additional approaches for those not reaching treatment goals 1. In the context of real-life clinical medicine, trying a dual GIP and GLP-1 receptor agonist, such as tirzepatide, is a reasonable next step for patients who do not achieve adequate weight loss with GLP-1 receptor agonists alone, considering its potential benefits and synergistic effects on weight loss and metabolic function 1.
From the Research
Glucagon-like peptide (GLP) receptor agonists and Glucose-dependent insulinotropic polypeptide (GIP) receptor agonists
- GLP-1 receptor agonists have been shown to improve glucose homeostasis, reduce body weight, and benefit cardiovascular health in type 2 diabetes mellitus (T2DM) 2, 3
- However, some individuals may not achieve adequate weight loss with GLP-1 receptor agonists, and alternative therapies may be considered
Dual GIP/GLP-1 receptor agonist therapy
- Dual GIP/GLP-1 receptor agonist therapy has been shown to produce profound weight loss, glycemic control, and lipid lowering in T2DM 2, 4
- This therapy may be considered for individuals who do not achieve adequate weight loss with GLP-1 receptor agonists alone
Combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA
- Combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA may be considered for most patients with T2D who do not have contraindications 4
- This combination addresses complementary pathophysiological mechanisms and enhances efficacy in achieving target haemoglobin A1C (HbA1c) levels
GLP-1 receptor agonists for the treatment of obesity
- GLP-1 receptor agonists have been shown to be effective in treating obesity, with significant weight loss and reduction in obesity-related complications 5
- GLP-1R agonists are promising agents for the treatment of obese individuals, with potential for further development and growing impact
GIP-derived GIP receptor antagonists
- GIP-derived GIP receptor antagonists, such as GIP(3-30)NH2, have been used to elucidate the molecular and cellular consequences of GIPR inhibition, desensitization, and internalization 6
- These antagonists may provide further insight into the role of the GIP system in health and disease, and enhance our understanding of the GIPR as a drug target