The effect of SGLT2i and GLP-1RA combination therapy in weight loss
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on December 5th, 2022
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The anti-diabetic medication, sodium-glucose cotransporter-2 inhibitors (SGLT2i), blocks glucose reabsorption in the kidney; this creates a calorie deficit and leads to weight loss. However, the rate of change is slower than predicted, and the loss can be reverted over time; this can potentially be explained by increased energy intake to compensate for the higher excretion. Glucagon-like peptide 1 receptor agonists (GLP-1RA) is another antidiabetic medication that acts on the central nervous system to suppress appetite. A recent study has investigated whether combining the two medications can create sustainable weight loss.
The study included 64 adults between the age of 18 and 75 who are obese (BMI > 27 kg/m2) and with relatively little change in their weight over the past 3 months. These patients had been diagnosed with type 2 diabetes and currently using metformin to treat their conditions. These 64 participants were randomly assigned into 4 treatment plans that last for 16 weeks: 1) SGLT2i dapagliflozin and placebo for exenatide; 2) GLP-1RA exenatide and placebo for dapagliflozin; 3) SGLT2i dapagliflozin and GLP-1RA exenatide; 4) placebo for both dapagliflozin and exenatide. Exenatide was injected twice daily; the initial dosage was set at 5 μg and was increased to 10 μg after 4 weeks. Patients were instructed to inject exenatide 15 to 30 minutes before breakfast and dinner. Dapagliflozin was also injected once daily at 8 pm.
By the 16th week of treatment, when compared to placebo, dapagliflozin reduced HbA1c by 0.5%, and GLP-1RA reduced HbA1c by 0.8%. The combination of SGLT2i and GLP-1RA is the most effective at reducing HbA1C by 1.2%. In terms of weight management, dapagliflozin is the only treatment that results in weight loss by an average amount of 1.2 kg after 10 days of treatment. By the end of the study, those in the SGLT2i group lost an average amount of 2.5 kg, and those in the exenatide group lost around 1.4 kg. Weight loss is the most significant in the group that used both SGLT2i and GLP-1RA, the average amount of reduction is 2.8 kg. As hypothesized, the weight loss is not due to appetite suppression because the amount of food intake is similar between the 4 groups on the 10th day and the 16th week. In fact, the study observed that the average amount of carbohydrate daily intake in those using dapagliflozin increased by 21.3 grams. The effect of medications on the central nervous system is the potential cause behind the weight loss. When subjected to pictures of high calorie food under fMRI scan, those who use both SGLT2i and GLP-1RA have less activity in the right amygdala, indicating less appetite. In terms of pharmacological safety, all treatments are relatively well-tolerated. However, the researchers noted that there is a statistically insignificant higher number of adverse events in the combination therapy group.
The study included 64 adults between the age of 18 and 75 who are obese (BMI > 27 kg/m2) and with relatively little change in their weight over the past 3 months. These patients had been diagnosed with type 2 diabetes and currently using metformin to treat their conditions. These 64 participants were randomly assigned into 4 treatment plans that last for 16 weeks: 1) SGLT2i dapagliflozin and placebo for exenatide; 2) GLP-1RA exenatide and placebo for dapagliflozin; 3) SGLT2i dapagliflozin and GLP-1RA exenatide; 4) placebo for both dapagliflozin and exenatide. Exenatide was injected twice daily; the initial dosage was set at 5 μg and was increased to 10 μg after 4 weeks. Patients were instructed to inject exenatide 15 to 30 minutes before breakfast and dinner. Dapagliflozin was also injected once daily at 8 pm.
By the 16th week of treatment, when compared to placebo, dapagliflozin reduced HbA1c by 0.5%, and GLP-1RA reduced HbA1c by 0.8%. The combination of SGLT2i and GLP-1RA is the most effective at reducing HbA1C by 1.2%. In terms of weight management, dapagliflozin is the only treatment that results in weight loss by an average amount of 1.2 kg after 10 days of treatment. By the end of the study, those in the SGLT2i group lost an average amount of 2.5 kg, and those in the exenatide group lost around 1.4 kg. Weight loss is the most significant in the group that used both SGLT2i and GLP-1RA, the average amount of reduction is 2.8 kg. As hypothesized, the weight loss is not due to appetite suppression because the amount of food intake is similar between the 4 groups on the 10th day and the 16th week. In fact, the study observed that the average amount of carbohydrate daily intake in those using dapagliflozin increased by 21.3 grams. The effect of medications on the central nervous system is the potential cause behind the weight loss. When subjected to pictures of high calorie food under fMRI scan, those who use both SGLT2i and GLP-1RA have less activity in the right amygdala, indicating less appetite. In terms of pharmacological safety, all treatments are relatively well-tolerated. However, the researchers noted that there is a statistically insignificant higher number of adverse events in the combination therapy group.