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Greater Weight Loss Found With SGLT-2 Inhibitors Than GLP-1 RAs in Patients with T2D

Aug 7, 2021
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Kornelia Ilias, Pharm.D. Candidate, Creighton University School of Pharmacy and Health Professions

Contrary to previous studies, new research finds SGLT-2i more effective for weight loss than GLP-1 RAs as add-on therapy to Metformin. 

Patients with T2D frequently struggle with excess weight, contributing to the development of comorbidities and worsened outcomes. Guidelines from the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) recommended using patient-specific parameters for selecting additional therapy after Metformin. Choosing medications with a built-in weight loss component may be advantageous, lowering insulin sensitivity and improving glucose control. Either SGLT-2 inhibitors or GLP-1 receptor agonists have been recommended as add-on medications to aid with weight loss. A previous meta-analysis from 2016 found that when combined with background metformin, GLP-1 receptor agonists (liraglutide, albiglutide, dulaglutide, or lixisenatide) produced an average loss of 2-5 kg compared to SGLT-2 inhibitors (empagliflozin, canagliflozin, or Dapagliflozin) average loss of 1.5-3 kg.  


This study conducted a retrospective chart review from a level 3 medical home located in Buffalo, NY. The patients had T2D and were taking either a GLP-1 receptor agonist or SGLT-2 inhibitor with background diabetes therapy. Data included dose, concomitant weight changing diabetes/anti-hypertensive agents, steroid use, and antipsychotic use. In addition, participant age, gender, race, smoking status, height, weight, renal function values, HbA1c, BP, and Charlson Comorbidity Index (CCI) score was also recorded. The primary outcome examined the change in weight loss over six months. Secondary outcomes looked at differences in blood pressure, A1C levels, and renal function. Patients were excluded if they took concomitant comparator medications, had a history of obesity surgery, had no T2D noted in the chart, or were concurrently taking weight-changing nondiabetic medications. Categorical variables were logged as percentages, then compared using the chi-square or Fisher exact test.   

Continuous variables were logged as medians and compared with the Manne-Whitney U test.  

Researchers selected 73 out of 133 patient charts for analysis. Approximately 42% were taking an SGLT-2, and 58% were taking a GLP-1. Subjects showed no significant difference in demographics: male, age, white, black, smoker, baseline weight, BMI, eGFR, SCr, baseline A1C, BP, baseline heart rate, Charlson Comorbidity Index, contaminant medications.  

Around 70% in both groups received background Metformin, with the remainder taking sulfonylurea, thiazolidinedione, DPP-4 inhibitor, or insulin as co-therapy.  

Canagliflozin was the most prescribed SGLT-2 inhibitor (74%), followed by Dapagliflozin (16%) and Empagliflozin (10%).  Liraglutide was the most prescribed GLP-1 receptor agonist (64%), followed by Dulaglutide (26%), Exenatide extended-release (7%), and Exenatide (2%). At six months, SGLT-2 inhibitor median weight loss was 2.80 kg (IQR -5.40 to -1.5) and GLP-1 receptor agonist median weight loss was 1.15 kg (IQR -3.38 to 0.975) (P= 0.014). There was no statistically significant difference between A1C (p= 0.865), eGFR (p= 0.617), SCR (p=0.058) and blood pressure (p= 0.841). The dose of GLP-1 receptor agonist showed no effect on primary or secondary outcomes. 

Contrary to previous studies, researchers found that individuals taking SGLT-2 inhibitors had significantly more weight loss than GLP-1 receptor agonists. The different outcomes might have resulted from utilizing a retrospective design and including multiple background therapies. Weaknesses of the study included having a variable follow-up window of +/- 90 days. Weight changes might have been affected by the time lab workup and weights were taken. The SGLT-2 inhibitor group might have had more outliers since 25.8% of the cohort had a weight loss of 5% or more, yet no participant had a weight gain of 5% or more. 

In contrast, the GLP-1 receptor agonist group had two outliers gaining and four losing 5% or more of their baseline weight. Some patients in the SGLT-2 inhibitor group were also prescribed weight-neutral DPP-4 inhibitors. More patients in the GLP-1 receptor agonist group were also taking insulin, a weight-gaining medication. Confirming these findings can be done by conducting another study with a larger, more diverse sample.  

Practice Pearls: 

  • Following Metformin, either SGLT-2 inhibitors or GLP-1 receptor agonists are add-on weight loss medications for patients with T2D. 
  • After six consecutive months of therapy, the trial participants lost weight with either the SGLT-2 inhibitor or the GLP-1 receptor agonist.  
  • Patients on an SGLT-2i had statistically more weight loss than those taking a GLP-1 receptor agonist when combined with background diabetes therapy consisting mainly of Metformin. Other background co-therapy included sulfonylurea, a thiazolidinedione, DPP-4 inhibitor, or insulin.  


Frieling, Katherine et al. “Weight loss differences seen between glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for the treatment of type 2 diabetes.” Journal of the American Pharmacists Association: JAPhA, S1544-3191(21)00283-1. June 17. 2021, doi:10.1016/j.japh.2021.06.015 

Kornelia Ilias, Pharm.D. Candidate, Creighton University School of Pharmacy and Health Professions 


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