Effects of Empagliflozin + Linagliptin vs Metformin + Insulin Glargine on Renal and Vascular Changes in Type 2 Diabetes

What Was Tested

The trial (phase 3) is built around Insulin Glargine.

However, in studies with patients suffering from diabetes mellitus type 2 (DM 2), early changes and impairments in large and small blood vessels as well as organ damage (e. g. to the kidneys) have been only insufficiently investigated (1).

The newest substance class in oral antidiabetics, i. e.

It had two arms (groups): Empagliflozin and Linagliptin (active comparator) and Metformin and Insulin sc (active comparator).

The registry classes the interventions as drug.

More on the Plan

Diabetes mellitus, considered at the beginning as a metabolic disorder, mutates into a predominantly vascular disease, once its duration extends over several years or/and when additional cardiovascular (CV) risk factors coexist, in particular arterial hypertension.

These parameters are only infrequently measured in studies with type 2 diabetes (9), mainly due to lack of expertise required to assess these vascular and renal markers, and lack of awareness that vascular changes are the key prognostic factor in type 2 diabetes.

In parallel to glucosuria, sodium is excreted in the urine and loss of sodium leads to a less reactive contraction of the small arteries in response to sympathetic activity, angiotensin II and catecholamines.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, the other new drug class of antidiabetic agents, are also attractive agents to treat type 2 diabetes.

Who Took Part

The registry lists 101 actual participants took part.

It was open to people of any sex aged from 18 years up to 75 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Male and female patients (females of child bearing potential must be using adequate contraceptive precautions). Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at screening visit. Informed consent (§ 40 Abs. 1 Satz 3 Punkt 3 AMG) has to be given in written form.

The full record lists 5 inclusion and 23 exclusion criteria; among the exclusions: any other form of diabetes mellitus than type 2 diabetes mellitus; use of insulin, glitazone, gliptin or sglt-2 inhibitor within the past 2 months; any history of stroke, transient ischemic attack, instable angina pectoris, or myocardial infarction within the last 6 months prior to study inclusion.

How the Study Was Run

It was run as a randomized, parallel-group and open-label study.

The participants were allocated by chance, so the Insulin Glargine group and the comparison group should start out alike.

The Insulin Glargine group and the comparison group ran side by side rather than switching.

Nothing was hidden in this open-label Insulin Glargine study: the participants and staff both knew the treatment.

It started in 2016-04 with completion listed for 2018-11-07.

It ran at 1 site in Germany.

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Effect of empagliflozin plus linagliptin vs metformin plus insulin glargine on basal NO activity of renal vasculature (response of RPF (renal plasma flow) to L-NMMA (NG-monomethyl-L-arginine) infusion) (time frame: at baseline and after 3 months on empagliflozin plus linagliptin or metformin plus insulin glargine, respectively).

It also tracked 3 secondary outcomes, for example Changes in oxidative stress level of renal vasculature (response of RPF to vitamin C infusion), changes in intraglomerular resistances (Ra and Re) and Pglom and changes in albuminuria (urinary albumin to creatinine ratio [UACR]), assessed in the 24-hour urine.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Insulin Glargine in 101 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Insulin Glargine compound page, all human trials.