SGLT2i, Pioglitazone, and Ketone Production in T2D

Официальное название

Protocol lV: SGLT2 Inhibitors, Pioglitazone and Ketone Production in Type 2 Diabetes Mellitus

Обзор

To examine whether the empagliflozin-induced stimulation of EGP, lipolysis, and ketone production in T2D individuals can be blocked by pioglitazone (which has direct hepatic and adipose tissue effects).

Подробное описание

Participants: 64 T2D subjects with the same inclusion and exclusion criteria as Protocol 1. Subjects with hematuria are excluded.

Study Design: Infusions of 3-3H-glucose and 14C-glycerol are started and continued to study end (2 PM). Baseline blood samples for HbA1c (x2) and for plasma insulin, glucagon, glucose, FFA, BHB, AcAc, glycerol, and plasma 3-3H-glucose and 14C-glycerol specific activities are drawn at -30, -20, -10, -5, and 0 minutes for measurement of lipolysis, ketone production (plasma ketone levels), and EGP. Empagliflozin (25 mg) is ingested at time zero (9AM) and plasma samples for the above are obtained every 10-20 minutes.

Following completion of the above study, subjects will be randomized to one of four groups (16 per group) for 10 weeks: (1) empagliflozin, 25 mg/day, plus pioglitazone placebo; (2) pioglitazone, 15 mg/day, increased to 30 mg after 2 weeks plus empagliflozin placebo; (3) empagliflozin (25 mg/d) plus pioglitazone (15/30 mg/d); (4) empa placebo plus pio placebo. Subjects will return to the CRC every 1-2 weeks for interim medical history, to check medication compliance, and to measure plasma insulin, glucagon, glucose, FFA, glycerol, BHB, and AcAc levels. At week 10, subjects will return to the CRC at 6AM and the baseline study will be repeated. HbA1c will be measured twice during week 10.

Вмешательства

• Препарат Empagliflozin 25 MG
  A medication used in the management and treatment of type 2 diabetes mellitus. It is in the sodium-glucose co-transporter (SGLT-2) class of medications.
• Препарат Pioglitazone 15 mg increased to 30 mg after 2 weeks plus Empagliflozin Placebo
  Placebo-Inert tablet
• Препарат Empagliflozin 25 mg/d plus Pioglitazone (15/30 mg/d)
  Pioglitazone, a medication used in the management and treatment of type 2 diabetes mellitus. It is in the thiazolidinedione class of medications

Первичные конечные точки

• Endogenous Glucose Production (EGP) [Срок оценки: 0 and 300 minutes]

Критерии участия

Критерии включения

• Ages 30-75
• BMI (Body Mass Index) 21-45 kg/m2
• HbA1c = 7.0-11%
• eGFR (estimated glomerular filtration rate)> 60 ml/min/1.73m2
• Blood Pressure (BP)≤160/90 mmHg
• Participants must be in general good health based on medical history, physical exam, screening blood chemistries, CBC (Complete Blood Count), TSH/T4 (thyroid/thyroxine hormone), EKG (electrocardiogram), and urinalysis (UA)
• Stable body weight (±1.5 kg) over the last 3 months and must not participate in an excessively heavy exercise program
• Patients treated with diet, Sulfonylureas, Metformin, or Sulfonylureas/Metformin (Sulfo/MET)
• Participants receiving a Glucagon like peptide -1 receptor agonist (GLP1-RA) must be on a stable dose for at least three months prior to study enrollment.
• Participants receiving a Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitor) must be on a stable dose for at least two months prior to study enrollment.
• SGLT2 inhibitors must be discontinued at least two months prior to study enrollment.
• Statin therapy is permissible if the dose has been stable for at least 3 months

Критерии исключения

An individual who meets any of the following criteria will be excluded from participation in this study:

• Patients treated with Thiazolidinediones (TZDs), or Insulin are excluded.
• Patients taking medications other than Sulfonylureas/Metformin (SU/MET), stable dose of GLP1-RA and DPP4i known to affect glucose metabolism are excluded. Patients taking SGLT2i within 2 months of screening visit will be excluded from participating in this study, however they may be asked whether they would agree to discontinue the medication for two months to become eligible. (Please see clarification below.) \*
• Subjects with evidence of proliferative retinopathy or estimated glomerular filtration rate (eGFR) < 60 are excluded
• Women of childbearing potential are excluded unless they are taking/using appropriate contractive medications/devices \* Only participants who are taking SGLT2 inhibitors during the prescreening period will be asked to discontinue the medication at least two months prior to the screening visit. If they agree, they will return for an HbA1c measurement four weeks after stopping the SGLT2 inhibitor.

If their HbA1c rises to greater than 10%, treatment will be initiated with either metformin, a DPP-4 inhibitor, or a sulfonylurea. We do not anticipate any adverse effects during this initial period, provided the HbA1c remains below 10%.

HbA1c will be measured using a fingerstick test, which requires only a minimal amount of blood. No compensation will be provided during this phase.

After two months of medication discontinuation, participants will return for a screening visit. If they meet all eligibility criteria, they will be enrolled in the study and payment done by protocol.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Texas Diabetes Institute/UH — San Antonio

Идентификаторы

NCT: NCT07053319 · 20230457HU-504077 · R01DK024092

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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