What is the average HbA1c reduction for Glucagon-Like Peptide-1 (GLP1) medications and Sodium-Glucose Cotransporter 2 (SGLT2) medications in patients with Type 2 Diabetes Mellitus?

From the Guidelines

GLP-1 receptor agonists typically reduce HbA1c by 1 to 2% on average, while SGLT2 inhibitors generally lower HbA1c by 0.7-1.0% in patients with Type 2 Diabetes Mellitus. The HbA1c reduction varies based on baseline levels, with patients having higher initial HbA1c values typically experiencing greater reductions 1. Common GLP-1 medications include semaglutide, dulaglutide, liraglutide, and exenatide, which are administered as weekly or daily injections, with the exception of oral semaglutide. Popular SGLT2 inhibitors include empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin, taken as daily oral tablets.

• GLP-1 medications work by enhancing insulin secretion, suppressing glucagon release, slowing gastric emptying, and promoting satiety
• SGLT2 inhibitors prevent glucose reabsorption in the kidneys, increasing urinary glucose excretion Both medication classes offer additional benefits beyond glycemic control, with GLP-1s promoting weight loss and cardiovascular benefits, and SGLT2s providing heart failure and kidney protection 1. The most recent evidence suggests that the addition of GLP-1 RAs or the dual GIP and GLP-1 RA to metformin usually results in 1 to 2% lowering of A1C 1.

From the FDA Drug Label

The efficacy of OZEMPIC was compared with placebo, sitagliptin, exenatide extended-release (ER), and insulin glargine. In patients with type 2 diabetes mellitus, OZEMPIC produced clinically relevant reduction from baseline in HbA1c compared with placebo Monotherapy with OZEMPIC 0. 5 mg and 1 mg once weekly for 30 weeks resulted in a statistically significant reduction in HbA1c compared with placebo Table 3. Results at Week 30 in a Trial of OZEMPIC as Monotherapy in Adult Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Diet and Exercise HbA1c (%) Baseline (mean) 8.0 8.1 8.1 Change at week 30b -0.1 -1.4 -1.6 Difference from placebob [95% CI] -1.2 [-1.5, -0.9]c -1.4 [-1.7, -1. 1]c Table 4. Results at Week 56 in a Trial of OZEMPIC Compared to Sitagliptin in Adult Patients with Type 2 Diabetes Mellitus in Combination with Metformin and/or Thiazolidinediones HbA1c (%) Baseline (mean) 8.0 8.0 8.2 Change at week 56b -1.3 -1.5 -0.7 Difference from sitagliptinb [95% CI] -0.6 [-0.7, -0.4]c -0.8 [-0.9, -0. 6]c INVOKANA (canagliflozin) has been studied as monotherapy, in combination with metformin HCl, sulfonylurea, metformin HCl and sulfonylurea, metformin HCl and sitagliptin, metformin HCl and a thiazolidinedione (i.e., pioglitazone), and in combination with insulin (with or without other anti-hyperglycemic agents). Table 10: Results from 26-Week Placebo-Controlled Clinical Trial with INVOKANA as Monotherapy in Adults with Type 2 Diabetes Mellitus HbA 1C(%) Baseline (mean)7.978.068.01 Change from baseline (adjusted mean)0.14-0.77-1.03 Difference from placebo (adjusted mean) (95% CI) †-0.91 ‡ (-1.09; -0.73) -1.16 ‡ (-1.34; -0. 99) Table 11: Results from 26-Week Placebo-Controlled Clinical Trial of INVOKANA in Combination with Metformin HCl in Adults with Type 2 Diabetes Mellitus HbA 1C(%) Baseline (mean)7.967.947.95 Change from baseline (adjusted mean)-0.17-0.79-0.94 Difference from placebo (adjusted mean) (95% CI) †-0.62 ‡ (-0.76; -0.48) -0.77 ‡ (-0.91; -0. 64)

The average HbA1c reduction for GLP1 medications like semaglutide (OZEMPIC) is around -1.2% to -1.6% as monotherapy and -1.3% to -1.5% in combination with metformin and/or thiazolidinediones. The average HbA1c reduction for SGLT2 medications like canagliflozin (INVOKANA) is around -0.77% to -1.03% as monotherapy and -0.79% to -0.94% in combination with metformin HCl. Key points:

• GLP1 medications:
  • Monotherapy: -1.2% to -1.6% HbA1c reduction
  • Combination therapy: -1.3% to -1.5% HbA1c reduction
• SGLT2 medications:
  • Monotherapy: -0.77% to -1.03% HbA1c reduction
  • Combination therapy: -0.79% to -0.94% HbA1c reduction 2 and 3

From the Research

Average A1c Reduction for GLP1 and SGLT2 Medications

• The average A1c reduction for GLP1 medications and SGLT2 medications in patients with Type 2 Diabetes varies across studies.
• A study published in 2024 4 found that the GLP-1 group averaged a 0.65% reduction in A1c, while the SGLT-2 group averaged a 1.05% reduction.
• Another study from 2011 5 reported that GLP-1 agonists showed a statistically significant reduction in HbA(1c) compared to placebo, with 46% of patients achieving the HbA(1c) goal <7% for exenatide, 47% for liraglutide, and 63% for exenatide LAR.
• A 2017 study 6 discussed the complementary approach of combining SGLT2 inhibitors and GLP-1 receptor agonists, which may improve long-term outcomes for patients with Type 2 Diabetes, but did not provide specific average A1c reduction values.

Factors Associated with A1c Reduction

• A 2021 study 7 identified patient characteristics associated with a ≥1% A1c reduction, including GLP-1/SGLT-2 persistence, congestive heart failure comorbidity, phentermine dispensing, care management team enrollee, and higher baseline A1c.
• The same study found that characteristics associated with absolute A1c reduction included age, baseline A1c, care management team enrollee, GLP-1/SGLT-2 persistence, and phentermine dispensing.

Comparison of GLP-1 and SGLT-2 Medications

• The 2024 study 4 compared the effects of GLP-1 agonists and SGLT-2 inhibitors on A1c reduction, weight loss, and changes in insulin requirements, but found no statistically significant difference between the two groups.
• The 2017 study 6 discussed the potential benefits of combining SGLT2 inhibitors and GLP-1 receptor agonists, but did not provide a direct comparison of their effects on A1c reduction.