Dr. Ahmed
Cagrilintide Semaglutide (CagriSema) will soon enter the competition with Semaglutide and Tirzepatide for the management of Diabesity.
Semaglutide under all its formulations (Ozempic, Rybelsus, and Wegovy) and Tirzepatide (Mounjaro) are considered the blockbuster medicines for the management of diabetes and obesity (Diabesity in short).
With new drugs coming into the markets, companies now see that these latest drugs may even enter into competition with Bariatric Surgeries (Gastric Sleeve and Gastric Bypass).
Until now, bariatric surgery is considered the best treatment for diabesity and most bariatric surgeons claim that they can cure diabetes and other comorbid conditions like hypertension and dyslipidemias.
The average weight loss after bariatric surgical procedures is estimated to range between 40% and 60%.
Researchers speculate that weight loss with CagriSema (Cagrilintide Semaglutide) may approach 23% to 30% which is probably the highest degree of weight loss associated with any of the medical therapies.
What is CagriSema (Cagrilintide Semaglutide)?
CagriSema is Cagrilintide + Semaglutide. Cagrilintide is a long-acting amylin analog that has shown promising results in the management of diabetes and obesity.
Pramlintide is a short-acting amylin analog secreted by the beta-cells of the pancreas in the same granules as insulin. In both Type 1 and Type 2 diabetics, along with insulin, pramlintide production is also reduced.
In humans, pramlintide, and Cagrlinitide, a long-acting amylin analog, lower blood glucose by the following mechanisms:
- It reduces post-meal glucose and suppresses cravings and hunger by slowing the release of gastric contents into the small intestine. It delays gastric emptying.
- Pramlintide also inhibits glucagon release from the alpha cells of the pancreas and therefore inhibits glucose production by the liver (gluconeogenesis).
- It also suppresses hunger by the central neuronal pathways.
Cagrilintide has a half-life of about 159 to 195 hours, unlike pramlintide which has a half-life of 48 to 55 minutes. It reaches the maximum plasma concentration in about 24 to 72 hours.
Here is a comparison between Pramlinitide and Craglinitide:
Cagrilintide | Pramlintide [Ref] | |
| Class | Long-acting Amylin analog | Short-acting Amylin analog |
| Brands | Not marketed yet | Symlin |
| FDA Approved | No | Yes (2005) |
| Indications | Being studied for the management of Type 2 Diabetes and Obesity | Both Type 1 and Type 2 Diabetes |
| Dosing | May range from 0.3 to 4.5 mg weekly | Type 1 diabetes:
Type 2 diabetes:
|
| Half-life | 159 to 195 hours | 48 to 55 minutes |
Effectiveness of Cagrilintide Semaglutide (CagriSema) in Diabetics:
A phase 2 trial evaluated the efficacy of CagriSema in obese diabetic patients who were on metformin +/- SGLT2 inhibitors.
Patients were divided into three groups in a 1:1:1. One group received CagriSema, the second group received Semaglutide, and the third received Cagrilintide.
Patients were given these drugs once weekly and titrated to a maximum dose of 2.4 mg weekly. The effects on A1C and body weight were evaluated after 32 weeks.
Here is a summary of the results:
CagriSema | Semaglutide | Cagrilintde | |
| A1C reduction | -2.2 | -1.8 | -0.9 |
| Weight loss | -15.6% | -5.1% | -8.1% |
| FBG | -3.3 mmol/l | -2.5 mmol/L | -1.7 mmol/l |
| Adverse events | 68% | 71% | 80% |
As can be seen in the tablet above, CagriSema (Cagrilintide Semaglutide) resulted in a significantly greater A1C reduction vs Semaglutide and Cagrilintide.
Similarly, the weight loss effects of CagriSema were also amazing. People in the CagriSema group lost 15.6% of weight vs. 5.1% and 8.1% with Semaglutide and Cagrlintide respectively.
In addition, the adverse events were comparable in all three groups, slightly favoring CagriSema.
Effectiveness of CagriSema (Cagrilintide Semaglutide) as a weight loss drug:
In a Phase 1B Trial, CagriSema was evaluated to see how safe it is compared to a placebo drug at different doses in overweight and obese individuals without other medical conditions.
Participants were administered Cagrlinitide in different strengths 0·16 mg, 0·30 mg, 0·60 mg, 1·2 mg, 2·4 mg, or 4·5 mg weekly or a placebo medicine. All participants also received Semaglutide titrated to a dose of 2.4 mg weekly.
The weight loss estimated at week 20 was greater in patients who received Cagrilintide Semagluide than Placebo Semaglutide treatment:
Drugs and Dosage | Weight Loss | % Difference Vs Placebo |
| Cagrilintide Semaglutide 1.2 mg | 15.7% | 6% |
| Cagrilintide Semaglutide 2.4 mg | 17.1% | 7.4% |
| Placebo Semaglutide 2.4 mg | 9.8% | – |
Participants in the Cagrilintide Semaglutide lost significantly more weight (15.7% – 17.1%) at different doses vs Semaglutide placebo (9.8%)
The most common side effects were GI related. 96% of the participants in the CagriSema group and 97% in the placebo group reported side effects with 37% reporting GI-related side effects.
Higher doses of CagriSema were also evaluated against Semaglutide 2.4 mg (Wegovy) and the results favored CagriSema. Here is a summary:
Dose | Weight Loss | % Difference Vs Placebo |
| Cagrilintide Semaglutide 4.5 mg | 15.4% | 7.4% |
| Placebo Semaglutide 2.4 mg | 8% | – |
Effectiveness of Cagrilintide (Without Semaglutide) for Weight Loss Vs Liraglutide:
In a multicentered Phase 2 trial, obese individuals who had a BMI of 30 kg/m² or more without diabetes or 27 kg/m² or more with hypertension and high cholesterol were enrolled to receive Cagrlinitide once weekly at different doses, Liraglutide 3 mg (Saxenda) daily or matching placebo.
Cagrlintide monotherapy (without Semaglutide) was superior to placebo and resulted in 3 – 7.8% greater weight loss vs placebo. Here is a summary of the results:
| Drug | % Weight Loss | Weight Loss in Kgs | % Difference Vs Placebo |
| Cagrilintide 0.3 to 4.5 mg | 6 – 10.8% | 6.4 – 11.5 | 3 – 7.8% |
| Placebo | 3% | 3.3 |
High-dose Cagrilintide 4.5 mg (titrated gradually to the 4.5 mg dose) administered weekly was evaluated and found to be more effective than Liraglutide 3 mg daily (Saxenda).
The results of the table are summarized in the table below:
| Drug | % Weight Loss | Weight Loss in Kgs | % Difference Vs Liraglutide |
| Cagrilintide 4.5 mg | 10.8% | 11.5 | 1.8% |
| Liraglutide 3 mg | 9% | 9.6 |
In a nutshell:
Cagrilintide is a long-acting, once-weekly administered amylin analog. Its use in obese and diabetic individuals has been shown to have significant glucose-lowering and weight-losing effects.
However, when given combined with Semaglutide, and CagriSema, it is superior to Ozempic, Wegovy, Tirzepatide, and Saxenda, and will probably be the most potent diabetes and obesity drug.
CagriSema may be used as one of the most potent medical treatments for diabesity. In addition, more people may opt for medical Vs Surgical therapy because of the non-invasive nature and the long-term weight loss effects.
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