Sodium-glucose co-transporter 2 inhibitors (SGLT2i), such as dapagliflozin, have emerged as effective medications for controlling type 2 diabetes. Beyond their primary function of regulating blood sugar levels, these drugs have shown promising cardiovascular benefits, suggesting a broader impact on insulin resistance. A key aspect of dapagliflozin's effects is its potential for weight loss, making it a valuable option for overweight or obese individuals with type 2 diabetes.
How Dapagliflozin Promotes Weight Loss
The mechanisms behind dapagliflozin-induced weight loss are multifaceted. Initially, the loss of weight is thought to stem from glycosuria, which leads to a net caloric output and a subsequent reduction in overall body volume. However, the sustained weight loss observed with dapagliflozin may be attributed to the reduction of visceral fat mass.
The Role of Abdominal Fat
Recent research has focused on the significance of specific abdominal fat depots and their connection to metabolic health. Structured ultrasound (US) imaging, or "eco-obesity," is a technique that allows for the measurement of five consecutive layers of abdominal fat: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om), and right perirenal (RK). Notably, PP, Om, and RK fat depots have been identified as predictors of metabolic syndrome (MS).
Clinical Evidence: Dapagliflozin's Impact on Abdominal Fat
A randomized, open-label, phase IV clinical trial known as the Omendapa trial (EudraCT: 2019-000979-16) investigated the effects of dapagliflozin on these specific fat depots. The study involved 29 patients with type 2 diabetes and obesity who were either treated with metformin alone (cohort A) or metformin in combination with dapagliflozin (cohort B).
Study Design and Methods
The trial included patients with type 2 diabetes diagnosed less than 12 months before randomization, and all participants were treatment-naive. Cohort A consisted of 14 patients treated with metformin alone, while cohort B included 15 patients treated with metformin and dapagliflozin. Anthropometric measures and laboratory tests were conducted at baseline, 3rd, and 6th months to assess changes in glucose levels, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP, and microalbuminuria (MAL). Abdominal fat layers were measured using structured ultrasound imaging.
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Key Findings
After 6 months, cohort A experienced a weight loss of -5.5 ± 5.2 kg (5.7% from initial weight), while cohort B showed a weight loss of -8.4 ± 4.4 kg (8.6%). Abdominal circumference decreased by -2.7 ± 3.1 cm in cohort A and -5.4 ± 2.5 cm in cohort B (p = 0.011). Both metformin alone (-19.4 ± 20.1 mm; -21.7%) and the combination of metformin and dapagliflozin (-20.5 ± 19.4 mm; -21.8%) significantly reduced omental fat.
Interestingly, perirenal fat loss was significantly greater in the cohort B group compared to cohort A. Correlations between omental fat and leptin/CRP/MAL, as well as between RK fat and HOMA-IR, were observed only in the metformin + dapagliflozin group.
Implications
The study findings suggest that both metformin and dapagliflozin can induce fat loss in layers associated with metabolic syndrome. However, the combined treatment appears particularly effective in reducing perirenal fat. These results highlight the potential of dapagliflozin, especially in combination with metformin, to target specific abdominal fat depots and improve metabolic health.
Dapagliflozin Dosage and Weight Loss
A systematic analysis of 8,545 patients with type 2 diabetes from 24 randomized controlled trials indicated a dose-dependent relationship between dapagliflozin and weight loss.
Dosage-Related Effects
Patients treated with 2.5 mg/day of dapagliflozin showed a maximal effect (Emax) of -3.04% in body weight change, with the time taken to reach half of this effect (ET50) estimated at 30.8 weeks. Higher doses of 5, 10, and 20 mg/day resulted in Emax values of -6.57, -4.12, and -3.23%, respectively, and ET50 values of 27.3, 20.4, and 4.23 weeks, respectively. These data suggest that while higher doses may lead to a quicker initial weight loss, the overall maximal effect may vary.
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Factors Influencing Dapagliflozin's Weight Loss Effects
Several factors can influence the effectiveness of dapagliflozin in promoting weight loss. A study involving 200 Korean patients with type 2 diabetes identified key predictors of clinically meaningful weight reduction (≥3% decrease in body weight) after one year of dapagliflozin treatment.
Predictors of Weight Loss
The likelihood of achieving a weight loss of ≥3% was significantly increased with:
- Regular exercise (OR 2.13, 95% CI 1.07-4.25)
- Concomitant metformin treatment (OR 2.90, 95% CI 1.23-6.80)
- Normal renal function (OR 13.84, 95% CI 1.33-144.26)
Conversely, patients treated with sulfonylurea were less likely to experience this level of weight loss (OR: 0.39, 95% CI: 0.19-0.79).
Implications for Treatment
These findings suggest that lifestyle factors, concomitant medications, and renal function play a significant role in determining the weight loss benefits of dapagliflozin. Healthcare providers can use this information to tailor treatment plans and optimize outcomes for patients with type 2 diabetes.
Additional Benefits of Dapagliflozin
Beyond weight loss, dapagliflozin offers several other benefits for individuals with type 2 diabetes and heart failure.
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Improved Glycemic Control
Dapagliflozin works by inhibiting the SGLT2 protein in the proximal tubule of the kidney, leading to the excretion of excess glucose through urine. This mechanism helps to lower blood sugar levels and improve glycemic control.
Cardiovascular Benefits
Studies have demonstrated that dapagliflozin can reduce the amount of work the heart has to do to pump blood around the body. This can improve symptoms of heart failure, such as breathlessness, tiredness, and swelling in the lower legs.
Long-Term Safety
Dapagliflozin is generally considered safe for long-term use. However, it is essential to consult with a healthcare provider before starting or stopping the medication.
Lifestyle Changes to Enhance Dapagliflozin's Effects
To maximize the benefits of dapagliflozin, individuals can incorporate several lifestyle changes:
- Healthy Diet: Focus on a balanced diet with plenty of fruits, vegetables, and whole grains. Limit sugary foods and drinks.
- Regular Exercise: Aim for at least 150 minutes of moderate-intensity exercise per week.
- Weight Management: If overweight or obese, strive to lose weight through a combination of diet and exercise.
- Limit Alcohol Consumption: Drink alcohol in moderation, if at all.
- Quit Smoking: If you smoke, consider quitting to improve overall health.
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