Beta Cell Function in Type 2 Diabetes: Differential Effects of SGLT2 Inhibitors and GLIP-Receptor Agonists

NCT07325435 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: 1876088 SUNY Downstate MedicalNew York Community Trust
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Minorities have higher rates of diabetes, poorer glucose control, and higher complications and mortality rates than white people. Several recently approved diabetes medicines improve cardiovascular and renal outcomes through two different mechanisms. This study will explore key determinants of blood glucose levels namely beta cell function after short-term randomized, parallel group treatment with FDA approved Glucagon-Like Peptide-1 Receptor Agonists¬ (GLP-1 RA), or FDA approved Sodium-Glucose co-Transporter-2 Inhibitor (SGLT-2i). Because diabetes in black people shows a unique ability to recover pancreatic insulin secretion, it is important to determine whether the effects of these drug classes differentially improve pancreatic beta cell function.

Conditions

Type 2 Diabetes (T2DM)

Keywords

Beta Cell Function; Type 2 diabetes; Black African American; Diabetes metabolism; GLP-1 receptor Agonist; SGLT-2 inhibitor; medication effects in Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change in Stimulated C-peptide Index during an Oral Glucose Tolerance Test is a measure of Beta Cell Function and will be measuresd at baseline and at 16 weeks after treatment with GLP-1 Receptor Agonist or SGLT2-Inhibitor

  Primary Outcome Measure: The stimulated c-peptide index a primary outcome measure and is measured at baseline and 16 weeks. Change in the stimulated c-peptide index is the 16 week value minus the baseline. Higher numbers of the c-peptide index indicate better beta cell function while lower numbers indicated worse beta cell function. The stimulated c-peptide index is a calculated ratio of the c-peptide (ng/ml) to glucose levels (mg/dl) used to assess pancreatic beta cell function. It is calculated as the incremental area under the curve (AUC) of plasma C-peptide divided by the incremental AUC of plasma glucose (∆C-peptide 0-120/∆ Glucose 0-120). The outcome measure of plasma c-peptide (ng/ml) and plasma glucose (mg/dl), during the OGTT (after an overnight fast) at -15, 0, 10, 30, 45, 60, 90 and 120 minutes are combined into one primary outcome variable.

  Baseline, 16 weeks

Secondary Outcomes (2)

• 1 . Title: Change in Glycemic Control Measured at Baseline and 16 Weeks of Treatment with GLP-1 receptor Agonist or SGLT-2 Inhibitors

  Baseline, 16 weeks

• Change in Body Weight from Baseline and 16 Weeks of Treatment with GLP-1 receptor Agonist or SGLT-2 inhibitors

  Baseline, 16 weeks

Study Arms (2)

GLP1-RA

ACTIVE COMPARATOR

We will examine the effect of GLP-1 RA on pancreatic beta cell function as measured by insulin, C-peptide and glucose serum concentrations during OGTT.

Drug: GLP1-RA

SGLT-2i

ACTIVE COMPARATOR

We will examine the effect of SGLT-2i on pancreatic beta cell function as measured by insulin, C-peptide and glucose serum concentrations during OGTT

Drug: SGLT-2 inhibitor

Interventions

SGLT-2 inhibitor DRUG

SGLT-2 inhibitors block the SGLT-2 receptor

Also known as: empagliflozin (Jardiance®), dapagliflozin (Farxiga®), canagliflozin (Invokana®), bexagliflozin (Brenzavvy®)

SGLT-2i

GLP1-RA DRUG

GLP-1 RAs stimulate the GLP-1 Receptor

Also known as: liraglutide (Victoza), semaglutide (Ozempic), dulaglutide (Trulicity)

GLP1-RA

Eligibility Criteria

• Age: 24 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agrees to participate (signs and dates the informed consent) and agrees to all study procedures and conditions of the protocol.
• Black (self-identified) patients with relatively recent onset (\< 15 years) DM2
• aged \>= 24 years of age (adults \< age 24 years old need additional resources to consistently participate, and may have different metabolism)
• HbA1c between 6.9% and 10%, inclusive
• BMI \> 23 and \< 45 kg/m2, and stable body weight over 2 months

You may not qualify if:

• Currently taking no diabetes medication or on stable doses (2 months) of metformin or metformin plus sulfonylureas without additional diabetes medication(s).
• Ability to take and agree to taking oral medication and to self-inject
• For persons of reproductive potential: negative pregnancy test, use of effective contraception for at least 1 month prior to screening, and agreement to use such a method during study participation, and for an additional 4 weeks after completing the use of the study drug. They will be counseled that if they wish to become pregnant, they should follow the standard practice of optimizing their blood glucose in preparation for pregnancy. Use of these study drugs are not considered standard of care for diabetes during pregnancy. Effective contraception includes tubal ligation, hysterectomy, oral, implanted or injected contraceptives, mechanical (IUD) and barriers (diaphragm, condoms, spermicides) methods.
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout the study, including following a diabetic diet and maintaining a physical activity program
• Poor general health, low kidney function (eGFR \< 45), abnormal liver blood tests (AST and ALT \> 3 times the ULN, Bilirubin 2 x ULN), serious cardiovascular, liver or renal disease, known proliferative retinopathy, type 1 diabetes, pancreatitis or pancreas cancer, medullary thyroid cancer, MEN2 (or family history of MEN2), current low hematocrit (\< 35% for men and 33% for women, frailty, at risk for falls, current (past six months) alcohol or substance use disorder, history of a non-traumatic bone fracture, amputation, organ transplant, HIV or COVID, or if the patient cannot complete study activities.
• Current regular use of DDP-4 inhibitors, insulin or GLP-1 RA or SGLT2-inhibitors
• Currently pregnant, planned pregnancy in the next 7 months or nursing/lactating.
• Known allergic reactions to either the study medication
• Treatment with another investigational drug or other intervention within 4 months, or plan to enroll in another interventional study during their participation in this study
• Planned major surgery
• Recent (within 6 months): MI, Stroke, Cerebrovascular accident or unstable angina or revascularization procedures, grade 3 or 4 heart failure
• Use of weight loss medication, weight loss surgery.
• Use of glucocorticoids for chronic illness within 8 weeks prior to screening or likely to begin glucocorticoids during study period
• Study doctor considers subject a poor study candidate
• Cancer - History of active or untreated malignancy or in remission from a clinically significant malignancy for \< 5 years; exception: basal cell carcinoma of the skin.

Sponsors & Collaborators

• MaryAnn Banerji: lead
• The New York Community Trust: collaborator

Study Sites (1)

SUNY Downstate Health Sciences University

Brooklyn, New York, 11203, United States

Location

Related Publications (11)

• McGill JB, Subramanian S. Safety of Sodium-Glucose Co-Transporter 2 Inhibitors. Am J Cardiol. 2019 Dec 15;124 Suppl 1:S45-S52. doi: 10.1016/j.amjcard.2019.10.029.

  PMID: 31741440 BACKGROUND

• Ali AM, Mari A, Martinez R, Al-Jobori H, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Improved Beta Cell Glucose Sensitivity Plays Predominant Role in the Decrease in HbA1c with Cana and Lira in T2DM. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa494. doi: 10.1210/clinem/dgaa494.

  PMID: 32745202 BACKGROUND

• Mari A, Nielsen LL, Nanayakkara N, DeFronzo RA, Ferrannini E, Halseth A. Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea. Horm Metab Res. 2006 Dec;38(12):838-44. doi: 10.1055/s-2006-956505.

  PMID: 17163361 BACKGROUND

• Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E. Meal and oral glucose tests for assessment of beta -cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1159-66. doi: 10.1152/ajpendo.00093.2002. Epub 2002 Aug 6.

  PMID: 12388151 BACKGROUND

• Mari A, Tura A, Gastaldelli A, Ferrannini E. Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation. Diabetes. 2002 Feb;51 Suppl 1:S221-6. doi: 10.2337/diabetes.51.2007.s221.

  PMID: 11815483 BACKGROUND

• Rasouli N, Younes N, Utzschneider KM, Inzucchi SE, Balasubramanyam A, Cherrington AL, Ismail-Beigi F, Cohen RM, Olson DE, DeFronzo RA, Herman WH, Lachin JM, Kahn SE; GRADE Research Group. Association of Baseline Characteristics With Insulin Sensitivity and beta-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort. Diabetes Care. 2021 Feb;44(2):340-349. doi: 10.2337/dc20-1787. Epub 2020 Dec 17.

  PMID: 33334808 BACKGROUND

• Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009 Apr;58(4):773-95. doi: 10.2337/db09-9028. No abstract available.

  PMID: 19336687 BACKGROUND

• Banerji MA, Chaiken RL, Huey H, Tuomi T, Norin AJ, Mackay IR, Rowley MJ, Zimmet PZ, Lebovitz HE. GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. Diabetes. 1994 Jun;43(6):741-5. doi: 10.2337/diab.43.6.741.

  PMID: 8194658 BACKGROUND

• Banerji MA, Chaiken RL, Lebovitz HE. Long-term normoglycemic remission in black newly diagnosed NIDDM subjects. Diabetes. 1996 Mar;45(3):337-41. doi: 10.2337/diab.45.3.337.

  PMID: 8593939 BACKGROUND

• Hakim O, Bonadonna RC, Mohandas C, Billoo Z, Sunderland A, Boselli L, Alberti KGMM, Peacock JL, Umpleby AM, Charles-Edwards G, Amiel SA, Goff LM. Associations Between Pancreatic Lipids and beta-Cell Function in Black African and White European Men With Type 2 Diabetes. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1201-1210. doi: 10.1210/jc.2018-01809.

  PMID: 30407535 BACKGROUND

• Banerji MA, Chaiken RL, Gordon D, Kral JG, Lebovitz HE. Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive? Diabetes. 1995 Feb;44(2):141-6. doi: 10.2337/diab.44.2.141.

  PMID: 7859931 BACKGROUND

Related Links

• accessdataFDA.gov ( PDRs) of the medicine Empagliflozin
• accessdataFDA.gov ( PDRs) of the medicine liraglutide.
• accessdataFDA.gov ( PDRs) of the medicine semaglutide.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sodium-Glucose Transporter 2 Inhibitors; empagliflozin; dapagliflozin; Canagliflozin; bexagliflozin; Liraglutide; semaglutide; dulaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mary Ann Banerji, MD

  SUNY DOwnstate Health Sciences Center, Brooklyn, New York 11203

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Endocrinologist

Model Details: Participants will be randomized to marketed SGLT-2 inhibitors including empafliflozin or dapagliflozin versus GLP-1 receptor agonists (semaglutide, liraglutide or dulaglutide). The specific member of the class will determined by insurance copberage, pharmacy availablility or patient preference.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 8, 2026
• Study Start: December 21, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)