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Global Translational Medicine Incretins and cardiorenal disease

to an observational retrospective matched cohort study, of T2DM, there remains a gap in understanding the
semaglutide was associated with an increased risk of non- impact of incretin mimetics in reducing CKM risk in
arteritic anterior ischemic optic neuropathy, and future pre-diabetic patients post-intervention. In addition,
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studies to assess causality were proposed. Well-designed although lifestyle modification should be the cornerstone
trials powered for microvascular outcomes are warranted of therapy, innovative incretin therapeutics may have
to clarify associations between incretin therapies and a significant impact, given the concurrent weight loss
microvascular diseases. outcomes as well.

Previous meta-analyses of RCTs suggested an Incretin mimetics simulate the incretin hormone
association between the use of GLP-1 receptor agonists and function to return blood glucose levels to the euglycemic
retinopathy in patients with T2DM. However, conflicting range. More recently, a study demonstrated how
results from additional studies challenge these findings. endogenous levels of gut incretin hormones change
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According to a recent systematic review and meta-analysis as pre-diabetes advances to diabetes or regresses to
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of RCTs comparing the effect of SGLT-2i, GLP-1 receptor normoglycemia. Based on contemporary data, evidence
agonists, and dipeptidyl peptidase-4 inhibitors (DPP-4i) indicates that early intervention, targeting not only the
on the risk of diabetic retinopathy in patients with T2DM, GLP-1 receptor but also the GIP and glucagon receptors, is
Malyszczak and colleagues highlighted the challenges imminent. Now is the time to implement and disseminate
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in concluding that these newer antidiabetic drugs differ these therapeutics to tackle T2DM in its earlier phases,
substantially in their effect on diabetic retinopathy ensuring physiologic β-cell function and promoting
complications. Currently, the data advises caution with the weight reduction. Furthermore, these are therapeutic
use of DPP-4 inhibitors and semaglutide, especially among targets that could potentially be implemented in patients
patients with underlying retinopathy. diagnosed with pre-diabetes to hinder the progression
Given the innovative therapeutics being developed to T2DM. Most recently, the emerging benefits of
and studied for T2DM and obesity, the data support the GLP-1 receptor agonists, beyond glucose control, have
implementation of these medications in clinical studies reportedly impacted not only CKM conditions but OSA
as well. Shifting from sedentary habits and overnutrition
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to potentially treat pre-diabetes and obesity early on to increased physical activity and reduced nutrient
as a preventative measure to halt the progression to intake leads to weight loss, subsequent euglycemia,
overt T2DM. With the increasing prevalence of these and improvements in CKM outcomes. Future research
co-morbidities and the frequent association of obesity directions should focus on how incretin mimetics affect
with CKM syndrome, the effective weight loss and HbA1c
reduction achieved with incretin mimetics may also benefit individualized responses to treatment of obesity and
CKM syndrome by evaluating their interactions with
patients with pre-diabetes, offering cardioprotective and endocrine cells, the nervous system, genetic makeup, and
hepatic steatosis-reducing properties. Although the early the composition and intake of nutrients.
results are encouraging, the mechanisms of action of
incretin hormones on various organs and systems remain Acknowledgments
inconclusive.
None.
Overall, incretin mimetics offer many positive effects
to negate the progression of diabetes. Besides the glucose- Funding
lowering properties of incretin mimetic, both the reduction
of appetite and food intake result in weight loss, thereby None.
proposing a feasible mechanism of action for diabetes Conflict of interest
prevention. Although incretins’ efficacy for weight loss
and improvement in quality-of-life has been documented, The authors declare no conflicts of interest.
there is a gap in evidence among patients with and without Author contributions
diabetes demonstrating a reduction in the risk of CVD
in the intervention phase or during chronic follow-up Conceptualization: Samar A. Nasser and Keith C. Ferdinand
care. 20,43,44 Writing – original draft: Samar A. Nasser
Writing – review & editing: All authors
6. Conclusion
Ethics approval and consent to participate
Although both therapeutic and lifestyle interventions
have demonstrated the benefit of reducing the incidence Not applicable.

Volume 4 Issue 1 (2025) 52 doi: 10.36922/gtm.4405