Clinical trial NCT02592421: SGLT2 Inhibition and Stimulation of Endogenous Glucose Production: Protocol 2
Official title: Protocol 2: Elucidation of Mechanisms Responsible for the Increase in EGP Following SGLT2 Inhibition: Decrease in Plasma Glucose Conc or Change in Islet Hormone (Glucagon/Insulin) Secretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type II Diabetes Mellitus
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-10-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In Protocol 2, the investigators will determine the role of pancreatic hormones (increase in plasma glucagon and decrease in plasma insulin concentration) in the stimulation of EGP following SGLT2 inhibition.

Detailed description: The inhibition of the renal (kidney) SGLT2 transporter has proven to be an effective therapeutic intervention to reduce plasma glucose levels (amount of glucose found in the liquid part of blood) and HbA1c.

In this study, the investigators hope to define the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration. The investigators will examine whether the signal for the increase in EGP (endogenous glucose production) caused by glucosuria (an excess of sugar in the urine, typically associated with diabetes) is mediated via the decrease in plasma glucose and insulin concentrations, or by the increase in plasma glucagon concentration.

Eligibility criteria: Inclusion Criteria:

* T2DM subjects
* 18 - 70 yrs old
* BMI = 25-45 kg/m2
* Must be on a stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea
* HbA1c \<10.0%
* Stable body weight (± 3 lbs) over preceding 3 months
* Do not participate in excessively heavy exercise

Exclusion Criteria:

* Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea)
* Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine \>1.4 females or \>1.5 males, or 24-hour urine albumin excretion \> 300 mg

Primary outcomes:
measure: Change in Plasma Glucose Concentration
timeFrame: Baseline to 240-300 minutes
measure: Change in Endogenous Glucose Production (EGP)
timeFrame: Baseline to 240-300 minutes
Secondary outcomes:
measure: Change in Plasma Insulin During Measurement of EGP
timeFrame: Baseline to 240-300 minutes
measure: Change in Glucagon During EGP Measurement
timeFrame: Baseline to 240-300 minutes
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Ralph A. DeFronzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alatrach M, Laichuthai N, Martinez R, Agyin C, Ali AM, Al-Jobori H, Lavynenko O, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors. Diabetes. 2020 Apr;69(4):681-688. doi: 10.2337/db19-0770. Epub 2020 Jan 8.