Page 18 - IMO-2-1

Innovative Medicines & Omics Incretin mimetics in diabetes management

and decreases in postprandial and fasting plasma glucose. GIP, and glucagon receptors. This unique mechanism
Studies have shown that, for HbA1c reduction, lixisenatide addresses both glycemic control and weight management,
is non-inferior to twice-daily exenatide and is generally making it particularly relevant in the treatment of obesity
well tolerated. 86 and T2DM. Recent clinical trials have demonstrated
The most commonly reported side effects of lixisenatide retatrutide’s potential to induce significant weight loss and
are gastrointestinal symptoms, such as nausea, vomiting, improve metabolic parameters in individuals with obesity
and diarrhea. These side effects are typically dose-dependent and T2DM. By acting on both glucose metabolism and
and often diminish in intensity within the first 3 – 6 weeks appetite regulation, retatrutide offers a promising avenue
of treatment. Immunogenic effects have been reported for enhanced patient outcomes. 89,90
with lixisenatide; patients who develop anti-lixisenatide In a Phase 2 clinical trial, retatrutide was administered
antibodies may experience a slightly higher frequency of to participants with a BMI of 30 or higher, resulting in
allergic responses and injection site reactions compared substantial weight loss over 24 weeks. Participants receiving
to those without antibodies. Routine antibody testing is retatrutide achieved an average weight reduction of 12 – 15%
not required, but patients may consider switching to an compared to the placebo group. In addition, improvements
alternative antidiabetic therapy if they experience significant in glycemic control were observed, with reductions in
glycemic control issues or persistent injection site reactions. 87 HbA1c levels and fasting plasma glucose. These trial results

When lixisenatide is introduced to existing regimens, such indicate that retatrutide not only promotes weight loss but
as basal insulin therapy or sulfonylurea treatment, adjustments also has a positive impact on associated metabolic disorders,
to all diabetes medications may be required to mitigate the positioning it as a compelling option for patients with obesity
risk of hypoglycemia. Although mild-to-moderate renal and T2DM. 91,92 The safety profile of retatrutide has been
impairment does not necessitate a dosage adjustment, close generally favorable, with most adverse events being mild–
monitoring is recommended, as these individuals may be to-moderate in severity. Common side effects included
more susceptible to adverse effects, such as dehydration, gastrointestinal symptoms such as nausea, diarrhea, and
which could deteriorate kidney function. Individuals with abdominal pain, which typically resolved with continued
severe renal impairment should be constantly monitored for treatment. Notably, the incidence of hypoglycemia was low,
worsening renal function and a higher likelihood of adverse a significant advantage over some existing therapies for
events, especially gastrointestinal issues. 86,88 T2DM. Although long-term safety and effectiveness are still
under investigation, initial findings suggest that retatrutide
4.8. Retatrutide may become a valuable addition to the therapeutic option
Retatrutide (Figure 9) is a novel investigational medication for obesity and T2DM, potentially improving patients’
designed as a triple-hormone RA, targeting the GLP-1, quality of life and metabolic health. 93

Figure 9. Chemical structure of retatrutide. Reproduced from Caturano et al. 94

Volume 2 Issue 1 (2025) 12 doi: 10.36922/imo.4911