Effectiveness of GLP-1 On Glycaemic Control, Weight, and Lipid Profile 

In today’s article, we’re going to be analyzing a study on the effectiveness of GLP-1 on patients with type 2 diabetes. 

Study highlights:

• It involved 39,246 participants
• Compared with placebo, tirzepatide proved to be the most effective GLP-1 drug for reducing haemoglobin and fasting plasma glucose concentrations
• It also significantly improved weight management for patients with type 2 diabetes

Introduction – Diabetes Epidemic

Diabetes quickly rose to the status of a global epidemic, affecting 476 million people in total; of these 476, 463 million have type 2 type diabetes. Of course, pharmacological trends are following suit, with more and more attention being diverted to Glucagon-like peptide-1 receptor agonists. The drugs are garnering this much attention because of their incredible effects:

• Insulin secretion control
• Glucagon secretion control
• Gastric emptying slowdown
• Caloric intake reduction
• Weight reduction

For these reasons, FDA approved several GLP-1 formulations to be used in diabetes 2 treatment and weight management. These are:

• Exenatide
• Liraglutide
• Dulaglutide
• Albiglutide
• Lixisenatide
• Semaglutide and
• Tirzepatide

Given the diversity of GLP-1 type drugs, their actions and dosage, a comprehensive study was needed to attest to their effectiveness and point out which drug will lead to the best possible outcomes.

Methods Of The Study And Its Goals

Given the number of different types of GLP-a drugs available, meant there was a need to study the effectiveness of each one individually. This involved several different networks of meta-analysis and the analysis of past large-scale studies targeting the following criterias:

• Effectiveness in weight reduction
• Glycemic control and
• Lipid profile

The search strategy employed for this specific study was a systematic review of the entire body of studies employing GLP-1 in diabetes management spanning between 17 December 2022 and 19 August 2023. 

The Results Of The Study

Once all the data was gathered, it was time to sort it screen and organize. A total of 16,316 papers were collected and, after filtering the duplicate, ineligible and inappropriate ones, a total of 76 remained. 

These were evaluated on the following criteria:

• Glycaemic control
• Body weight control
• Lipid concentration control

Glycaemic Control

When talking about glycaemic control, researchers are looking at glycated hemoglobin (HbA1c) reduction. Glycated hemoglobin, or HbA1c, is something that’s made when glucose (sugar) sticks to the red blood cells and increases your blood sugar levels.

This section of the study involved 26,343 test subjects divided into two groups – placebo and type 2 diabetes. All evaluated drugs showed significant efficacy, compared to the placebo and led to HbA1c reduction.

These were the 3 top performing drugs:

• Tirzepatide: This drug showed the most significant reduction in HbA1c levels.
  • Mean Difference: The average reduction in HbA1c was -2.10%.
  • 95% Confidence Interval: This means the true reduction in HbA1c is likely between -2.47% and -1.74%.
  • SUCRA: The Surface Under the Cumulative Ranking curve (SUCRA) value was 94.2%, indicating a high probability that this drug is among the most effective.
  • High Confidence: The evidence supporting this result is of high confidence.
• Mazdutide: The second most effective drug.
  • Mean Difference: The average reduction in HbA1c was -2.09%.
  • 95% Confidence Interval: The true reduction is likely between -3.10% and -1.09%.
  • SUCRA: The SUCRA value was 90.4%.
  • High Confidence: The evidence supporting this result is also of high confidence.
• CagriSema: The third most effective drug.
  • Mean Difference: The average reduction in HbA1c was -1.80%.
  • 95% Confidence Interval: The true reduction is likely between -2.87% and -0.73%.
  • SUCRA: The SUCRA value was 80.9%.
  • High Confidence: The evidence supporting this result is of high confidence.

Body Weight Control

Body weight control analysis involved 21,349 participants and 53 trials where the goal was to measure changes in body weight among the participants. 

The most effective drug was CagriSema, where the test subjects experienced a total weight loss of 14.03kg (30.93lbs). 

The list of other effective drugs in order of total weight loss are:

• Tirzepatide
• Retatrutide
• Orforglipron
• Semaglutide
• Liraglutide

When talking about total body weight reduction, we cannot skip over BMI. These are the most effective drugs in reducing the overall BMI in test subjects:

Tirzepatide:

• Effect on BMI: It lowered BMI by an average of -2.85 units.
• 95% Confidence Interval: The true reduction in BMI is likely between -3.70 and -2.01 units.

Orforglipron:

• Effect on BMI: It lowered BMI by an average of -2.06 units.
• 95% Confidence Interval: The true reduction in BMI is likely between -3.22 and -0.91 units.

Semaglutide:

• Effect on BMI: It lowered BMI by an average of -1.28 units.
• 95% Confidence Interval: The true reduction in BMI is likely between -1.73 and -0.83 units.

Liraglutide:

• Effect on BMI: It lowered BMI by an average of -0.81 units.
• 95% Confidence Interval: The true reduction in BMI is likely between -1.26 and -0.36 units.

Lipid Profiles

We evaluate serum lipid concentration on four accounts:

• High-Density Lipid Protein (HDL) – referred to as good cholesterol
• Low-Density Lipid Protein (LDL) – referred to as bad cholesterol
• Total Cholesterol – total amount of cholesterol (HDL and LDL)
• Triglycerides – fat found in the blood

Meta-analysis showed:

PEG-loxenatide:

• Effect on HDL: This drug significantly increased HDL concentrations compared to placebo.
• Mean Difference: The average increase in HDL was 0.16 mmol/L.
• 95% Confidence Interval: The true increase in HDL is likely between 0.00 and 0.31 mmol/L.

Semaglutide:

• Effect on LDL: This drug significantly lowered LDL levels.
  • Mean Difference: The average decrease in LDL was -0.16 mmol/L.
  • 95% Confidence Interval: The true decrease in LDL is likely between -0.30 and -0.02 mmol/L.
• Effect on Total Cholesterol: Semaglutide also significantly lowered total cholesterol levels.
  • Mean Difference: The average decrease in total cholesterol was -0.48 mmol/L.
  • 95% Confidence Interval: The true decrease in total cholesterol is likely between -0.84 and -0.11 mmol/L.

ITCA 650 and Tirzepatide:

• Effect on Triglycerides: Both drugs significantly lowered triglyceride levels compared to placebo.
  • ITCA 650:
    • Mean Difference: The average decrease in triglycerides was -1.59 mmol/L.
    • 95% Confidence Interval: The true decrease in triglycerides is likely between -2.86 and -0.32 mmol/L.
  • Tirzepatide:
    • Mean Difference: The average decrease in triglycerides was -0.89 mmol/L.
    • 95% Confidence Interval: The true decrease in triglycerides is likely between -1.64 and -0.13 mmol/L.

Conclusion

As evident in the study, GLP-1 type drugs proved much more effective than placebo in treating adults with type 2 diabetes and helping them manage their weight as well as cholesterol.

When we’re talking about glycemic control and BMI, tirzepatide was a clear winner, while the most effective overall weight loss drug was CagriSema. 

The study showed an overwhelming body of evidence into the effectiveness of GLP-1 medication and huge potential for the future. Though the actual drugs and combinations of drugs (blends), need to be studies further to ensure safe application.