Semaglutide Shows Comparable Glycemic Control Compared With Dulaglutide

Recent clinical evidence is challenging the long-standing medical consensus that type 2 diabetes (T2D) is a chronic, progressive, and irreversible condition. A significant real-world study published in BMC Endocrine Disorders highlights the effectiveness of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs), semaglutide (Ozempic, Wegovy) and dulaglutide (Trulicity), with structured nutritional interventions in patients who are treatment naïve.¹

“Although both agents are long-acting GLP-1 RAs, differences in molecular structure and pharmacokinetic properties may translate into clinically meaningful variations in glycemic and weight-related outcomes,” the study authors said.¹

This retrospective analysis, conducted in Istanbul, evaluated 106 adults with newly diagnosed T2D who were prescribed either semaglutide (1.0 mg) or dulaglutide (1.5 mg) alongside a hypocaloric diet of 1200 to 1400 calories per day. The findings suggest that for pharmacists and health care providers, the early initiation of these therapies may facilitate a paradigm shift from simple glucose management toward actual disease remission.¹

The success of these interventions is rooted in the "twin-cycle hypothesis," which posits that chronic energy excess leads to fat accumulation in the liver and pancreas, disrupting insulin signaling and beta-cell function. By inducing a sustained negative energy balance, patients can achieve a reduction in ectopic fat, which is the primary driver of normalized glycemic control.²

Although weight loss is the strongest predictor of remission, the choice of pharmacological adjunct plays a critical role. In the Turkish study, both semaglutide and dulaglutide achieved clinically meaningful reductions in hemoglobin A_1c levels, typically between 1.0 and 1.5 percentage points over 6 months. However, semaglutide demonstrated superior outcomes regarding weight reduction, with a median loss of 12 kg compared to 7.5 kg in the dulaglutide group.¹

Pharmacists should note the distinct molecular profiles that contribute to these clinical variations. Dulaglutide is a long-acting analog fused to a modified human immunoglobulin G4 Fc fragment, which reduces renal clearance and allows for once weekly administration. Semaglutide, while also once weekly, utilizes a fatty-acid side chain to enhance albumin binding and resist degradation. These structural differences likely explain why semaglutide was independently associated with a higher likelihood of patients achieving at least a 10% reduction in body weight.¹

Furthermore, semaglutide showed a more pronounced benefit in lowering low-density lipoprotein cholesterol, though it is important to remember that GLP-1 RAs are often insufficient to meet high-risk lipid targets without additional statin therapy.¹

“Both semaglutide and dulaglutide achieved clinically meaningful reductions in HbA1c levels,” the study authors said.¹ “Although baseline HbA1c values were higher in the dulaglutide group, the magnitude of HbA1c reduction over 6 months did not differ significantly between groups in unadjusted analyses.”

Safety and tolerability remain paramount considerations for pharmacists when counseling patients. Gastrointestinal adverse events were the most frequent complaints in both treatment groups, including nausea, constipation, and diarrhea. Interestingly, constipation was more prevalent in the dulaglutide group (29.4%) compared with the semaglutide group (10.9%), and nausea was slightly more common with semaglutide.¹

“The higher proportion of patients without reported adverse events in the semaglutide group should be interpreted cautiously given the nonrandomized and observational nature of the study,” the study authors said.¹

Rare but serious risks include pancreatitis and gallbladder disease, with 1 case of pancreatitis reported in the dulaglutide group that was likely related to underlying gallstones. Pharmacists must also be vigilant regarding thyroid tumor risks, as GLP-1 RAs are contraindicated in patients with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.^3,4

The definition of remission has recently been standardized as maintaining an A_1c below 6.5% for at least 3 months without the use of glucose-lowering medications. Evidence from the broader scientific community, including the DiRECT and DIADEM-I (NCT03225339) trials, confirms that remission is most achievable in individuals with a short duration of diabetes and relatively preserved beta-cell function.^2,5

For populations who are treatment naïve and newly diagnosed, the combination of GLP-1 RAs and caloric restriction offers a unique therapeutic window. As the role of the pharmacist evolves, the focus must remain on the early identification of eligible patients and the implementation of individualized, sustainable lifestyle modifications to ensure long-term metabolic health and potentially reverse the pathophysiology of T2D.¹

READ MORE: Diabetes Resource Center

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REFERENCES

1. Cetiner S. Comparative effectiveness of semaglutide and dulaglutide combined with hypocaloric diet in newly diagnosed type 2 diabetes: a retrospective real-world study. BMC Endocr Disord. Published online March 14, 2026. doi:10.1186/s12902-026-02232-y

2. Pescari D, Mihuta S, Bena A, Pui R, Paul C, Stoian D. Nutrition-induced remission of type 2 diabetes: mechanisms, clinical evidence, and future directions-a mini review. Front Clin Diabetes Healthc. 2026;7:1792614. Published 2026 Feb 20. doi:10.3389/fcdhc.2026.1792614

3. Mayo Clinic. Semaglutide (subcutaneous route). February 1, 2026. Accessed March 16, 2026. https://www.mayoclinic.org/drugs-supplements/semaglutide-subcutaneous-route/description/drg-20406730

4. Mayo Clinic. Dulaglutide (subcutaneous route). February 1, 2026. Accessed March 16, 2026. http://www.mayoclinic.org/drugs-supplements/dulaglutide-subcutaneous-route/description/drg-20122526

5. Juray S, Axen KV, Trasino SE. Remission of Type 2 Diabetes with Very Low-Calorie Diets-A Narrative Review. Nutrients. 2021;13(6):2086. Published 2021 Jun 18. doi:10.3390/nu13062086