Do Empagliflozin (Jardiance) and Dapagliflozin (Farxiga) affect appetite and satiety?

Effects of Empagliflozin and Dapagliflozin on Appetite and Satiety

Empagliflozin and dapagliflozin may initially increase appetite and food intake through alterations in central reward and satiety circuits, which helps explain why the observed weight loss with these medications is less than expected based on urinary calorie excretion.

Mechanisms of Action on Appetite

• SGLT2 inhibitors (including empagliflozin and dapagliflozin) cause weight loss primarily through renal energy loss and reduction in fat mass, with decreases in both visceral and abdominal subcutaneous adipose tissue 1
• Short-term studies show that dapagliflozin can increase central nervous system (CNS) activation in response to food cues in the early treatment phase (10 days), which may contribute to increased appetite 2
• This increased CNS activation in reward centers (particularly the left putamen) may explain why the actual weight loss observed with SGLT2 inhibitors is less than would be predicted based on urinary glucose excretion 2

Clinical Evidence on Appetite Effects

• In a randomized controlled trial examining empagliflozin's effects on appetite-regulatory peptides, no consistent changes in postprandial peptide-YY (PYY), glucagon-like peptide-1 (GLP-1), or acylated ghrelin were observed after 24 weeks of treatment 3
• Similarly, no significant changes in subjective appetite perceptions were reported with empagliflozin treatment 3
• The DAPA-DIET study found that after 12 months of dapagliflozin therapy combined with carbohydrate restriction, there were no significant changes in self-reported appetite despite significant weight loss (mean 8.1 kg) 4

Comparative Effects

• Both empagliflozin and dapagliflozin demonstrate similar effects on weight loss in clinical studies, though some comparative trials suggest empagliflozin may produce slightly greater weight reduction (2.9±6.4 kg vs 1.7±2.4 kg over 12 weeks) 5
• When dapagliflozin is combined with GLP-1 receptor agonists like exenatide, the GLP-1 agonist appears to blunt the increased CNS activation observed with dapagliflozin alone, potentially offering complementary effects on appetite regulation 2

Weight Loss Mechanisms

• The weight loss observed with SGLT2 inhibitors occurs despite potential increases in appetite, suggesting that the caloric loss through glucosuria outweighs any compensatory increase in food intake 1
• After longer-term treatment (16 weeks), the initial increase in CNS activation with dapagliflozin appears to normalize, suggesting potential adaptation in appetite regulation over time 2
• Weight loss with these medications is primarily due to fat mass reduction rather than changes in energy expenditure 4

Clinical Implications

• When prescribing empagliflozin or dapagliflozin, clinicians should be aware that patients may experience increased appetite, particularly in the early treatment phase 2
• Combining SGLT2 inhibitors with dietary interventions (such as carbohydrate restriction) may enhance weight loss outcomes without significantly increasing appetite 4
• For patients concerned about weight management, combining SGLT2 inhibitors with GLP-1 receptor agonists may provide complementary effects on appetite regulation 2, 6

Monitoring Considerations

• Regular monitoring of weight and discussing appetite changes with patients can help manage expectations and optimize treatment outcomes 4
• Patients should be informed about the potential for increased appetite, particularly during the initial weeks of treatment 2
• Despite potential appetite increases, these medications remain effective for weight management in patients with type 2 diabetes and obesity 1, 4

Additional Considerations

• SGLT2 inhibitors have broader benefits beyond glycemic control, including cardiovascular and renal protection, which should be considered in the overall treatment plan 1
• The weight loss effects of these medications are maintained even in vulnerable populations, such as elderly patients and those with signs of congestion 1
• Unlike many other diabetes medications, SGLT2 inhibitors do not require dose titration and have minimal effects on blood pressure, heart rate, or potassium levels 1