Dr. Ahmed Research into the impact of GLP-1 analogs on mortality rates has yielded significant findings for both diabetics and non-diabetic obese individuals.
Among the noteworthy GLP-1 analogs, Semaglutide, Liraglutide, and Dulaglutide have been extensively studied.
Results from various clinical trials and meta-analyses reveal pertinent data on the correlation between GLP-1 analog usage and all-cause mortality.
Semaglutide, a prominent GLP-1 analog, has demonstrated promising results in reducing mortality.
In the SUSTAIN-6 trial, semaglutide was associated with a significant reduction in cardiovascular events and all-cause mortality among diabetic patients.
Notably, semaglutide for heart failure and kidney disease showed a marked decrease in adverse outcomes, suggesting beneficial renal and cardiac effects beyond glucose regulation.
Comparative studies of semaglutide and other GLP-1 analogs like liraglutide and dulaglutide offer insights into varying efficacy levels.
The LEADER trial, which focused on liraglutide, also highlighted a reduction in all-cause mortality, albeit to a lesser extent than semaglutide.
Furthermore, dulaglutide, evaluated in the REWIND trial, exhibited a moderated effect on mortality, positioning it between semaglutide and liraglutide in terms of overall benefit.
The discrepancies in mortality rates observed across these medications may stem from several underlying mechanisms.
Semaglutide’s potent impact may be attributed to its better pharmacokinetic profile and stronger effect on glycemic control.
Additionally, semaglutide for longevity has shown potential due to its multifaceted benefits, including weight reduction, improvement in cardiovascular markers, and protective effects on kidney function.
While all these GLP-1 analogs contribute to improved survival rates, the nuanced differences underscore the importance of personalized treatment approaches.
Understanding the unique properties and benefits of each medication can aid healthcare providers in optimizing therapy for diabetic and non-diabetic obese individuals, ultimately enhancing patient outcomes and longevity.
A recent study evaluated the impact of GLP-1 analogs on mortality rates in individuals with immune-mediated inflammatory diseases.
Key points of the Study:
- A study has shown that GLP-1 receptor agonists (GLP-1RAs) lower the chances of death and serious heart problems in people with type 2 diabetes and immune-related inflammatory diseases (IMIDs).
- The researchers compared the effectiveness of GLP-1 RAs to dipeptidyl peptidase-4 inhibitors, a widely used medication class for type 2 diabetes.
- According to the study, patients who initiated treatment with GLP-1 RAs were associated with a significantly lower risk of death and MACE compared to those starting with DPP-4 inhibitors (Januvia and Galvus).
Immune-mediated inflammatory disease (IMID) occurs when the immune system mistakenly targets the body’s own tissues, resulting in inflammation, pain, and potential organ damage. Conditions like rheumatoid arthritis, psoriasis, and lupus are examples of IMID.
Type 2 diabetes is a long-standing medical condition marked by elevated blood sugar levels. It develops when the cells in the body become less responsive to insulin. Prolonged insulin resistance can damage blood vessels and nerves. With time, the person may become insulin deficient.
IMIDs and type 2 diabetes share a common risk factor for MACE, including heart attacks and stroke, due to the negative consequences of chronic inflammation and high blood sugar control on blood vessels. This can accumulate plaque, restricting blood flow to vital organs like the heart and brain.
A population-based study
GLP-1 RAs (Semaglutide, Liraglutide, Dulaglutide, and Exenatide) are drugs that mimic the effects of a natural hormone called glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic peptide or gastric inhibitory peptide)
These drugs help manage blood sugar levels, aid in weight loss, and reduce heart-related risks [ref] in people with type 2 diabetes.
However, their possible advantages for those with immune-related conditions like rheumatoid arthritis and psoriasis are still under investigation and need further study.
Recent research published on August 8, 2024, shows us positive results about the therapeutic power of glucose-like peptide-1 receptor agonists (GLP-1 RAs) for patients with both immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes.
The researchers studied the outcomes of patients initiating GLP-1 RAs or dipeptidyl peptidase-4 inhibitors (DPP-4is), revealing more benefits than we knew before.
The researchers studied a large group of people who had both inflammatory diseases (IMIDs) and type 2 diabetes (T2DM).
They compared two groups: one was treated with GLP-1 RAs, and the other with DPP-4 inhibitors (DPP-4is).
They focused on seeing if there were any differences in overall death rates and major heart-related problems (like heart attacks, strokes, and death from heart issues) between the two groups.
Methodology and analysis:
The study brought some exciting findings! It involved 10,855 participants and showed that patients who started taking GLP-1 RAs had a much lower risk of dying and experiencing serious heart problems, like MACE, compared to those who started taking DPP-4is.
The benefits were seen in many different groups, including people with various immune system conditions and heart health risks. Also, the reduction in risk was consistent across all these groups.
A remarkable discovery was that patients taking GLP-1 RAs had a much lower risk of dying from any cause.
Compared to DPP-4is, GLP-1 RAs lowered the risk of death by 52%, which is a new and useful conclusion. This means that GLP-1 RAs have more health benefits than just helping with blood sugar and heart health.
GLP-1 RAs have a double benefit: they not only reduce the risk of death but also lower the risk of major heart problems.
Patients on GLP-1 RAs were 34% less likely to experience heart attack, stroke, or cardiovascular disease compared to those on DPP-4is.
This is essential because people with immune-mediated disease (IMIDs) and type 2 diabetes already face a higher risk of heart disease.
The authors conducted a detailed analysis to determine how GLP-1 RAs affect specific types of MACE.
They found that these drugs reduce the risk of heart attacks, strokes, and cardiovascular diseases. This suggests that users may have broad benefits for heart health and protection against various heart-related risks.
Potential Mechanisms of Action
The exact processes by which GLP-1 RAs lower the risk of death and MACE in patients with IMIDs and type 2 diabetes are still unclear. However, several theories have been suggested.
One potential mechanism is that GLP-1 RAs may safeguard cardiovascular health by reducing inflammation as shown by a study from 2022, which is a major risk factor for CVDs.
With their anti-inflammatory properties, the drugs may defend the heart and blood vessels against damage, promoting overall cardiovascular well-being.
Another possible route is that GLP-1 RAs improve blood flow to the heart and essential organs.
By stimulating nitric oxide production [ref], GLP-1 RAs promote blood vessel relaxation and dilation, thereby improving blood flow. This improvement may lower the risk of heart attacks and stroke.
Lastly, GLP-1 RAs can reduce cardiovascular risk by optimizing blood sugar control. This is because raised serum glucose levels are a significant contributor to cardiovascular disease and those drugs effectively lower blood sugar. Through this decrease in glucose levels, the risk of any CVD is also reduced.
Conclusion:
This study result has considerable clinical implications for managing patient’s IMIDs and type 2 diabetes, showing that GLP-1 RAs are a more beneficial therapeutic strategy, than dipeptidyl peptidase-4 inhibitors (DPP-4is), especially for those with high cardiovascular risk.
It is important to remember that this study was observational, meaning it can not prove that GLP-1 RAs directly caused the benefits that were seen.
To confirm these findings and understand the exact role of GLP-1 RAs in managing IMIDs and type 2 diabetes, we need more reliable randomized controlled trials.
Meanwhile, the evidence of this study strongly supports the use of GLP-1 RAs in patients with IMIDs and type 2 diabetes.
These drugs are more effective in showing a notable decline in cardiovascular risk and mortality as compared to the DPP-4is.
