Stepping-down Approach in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?

NCT02846233 | Completed Results

• 1 other identifier: RDMSTEP
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

In traditional step-up approach, the patients with poorly-controlled type 2 diabetes are instructed to take up to 4 insulin injections daily or multiple daily injections (MDI) as the most advanced therapy. However, a significant number of these patients continue to have poor diabetes control. The most common reason is the noncompliance with multiple injections and the patient's reluctance to accept insulin-induced weight gain. More recently, the algorithm in diabetes management has significantly changed to accommodate the newer generation of medications. Addition of the diabetes medications, that can induce weight loss such as oral Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors and once-weekly glucagon-like peptide (GLP)-1 receptor agonists (GLP1 RA) injection, to a basal insulin is now recommended before the patient is advanced to MDI. This approach works very well in most patients since weight loss gives the patients an extra motivation to take medication regularly. Similarly, the patient does not require to take an insulin injection before each meal throughout the day in this approach. Unfortunately, there are still a large number of patients with poor glycemic control who are still on MDI. Some of them were initiated on MDI before the availability of newer generations of medications. Some were started simply because the physician was not aware of or not the familiar with the new recommendations. Regardless of the reason, these patients are likely to remain on MDI despite chronic poor glycemic control since the physicians are understandably reluctant to step down the most advanced insulin therapy. In addition, there has been no data on the benefits and safety of the stepping-down approach from the most advanced insulin therapy to the more patient-friendly approach that is the combined use of oral SGLT2i and once-weekly GLP1 RA injection.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in A1c at the End of Study Period

  change in A1c (%) from baseline to end of study at 16 weeks

  16 weeks (from baseline to end of study at 16 weeks)

Secondary Outcomes (7)

• Changes in Weight

  16 weeks (from baseline to end of study at 16 weeks)

• Changes in Blood Pressure

  16 weeks (from baseline to end of study at 16 weeks)

• Changes in Heart Rate

  16 weeks

• Changes in LDL

  16 weeks (from baseline to end of study at 16 weeks)

• Changes in Total Cholesterol

  16 weeks (from baseline to end of study at 16 weeks)

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

Interventions: All prandial insulin injections, usually 3 times daily before meals, will be discontinued. Basal insulin, usually once daily at bed time, will be continued at 80 % of the home dose. Albiglutide OR Dulaglutide AND Empagliflozin will be added to metformin and a basal insulin.

Drug: GLP1 receptor agonist; Drug: basal insulin; Drug: SGLT2 inhibitor; Drug: Metformin

Control group

NO INTERVENTION

Interventions: There will not be any change in insulin therapy, and they will continue to have the usual and standard care through the primary care provider. They should not receive SGLT2i and GLP1 RA during the study period.

Interventions

GLP1 receptor agonist DRUG

"Albiglutide or Dulaglutide" will be added to a basal insulin.

Also known as: Albiglutide (Tanzeum) or , Dulaglutide (Trulicity)

Treatment group

basal insulin DRUG

The participant will continue with the basal insulin.

Also known as: Lantus, Toujeo, NPH, levemir

Treatment group

SGLT2 inhibitor DRUG

"Empagliflozin" will be added to a basal insulin.

Also known as: Empagliflozin (Jardiance)

Treatment group

Metformin DRUG

The participant will continue with metformin.

Treatment group

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following patients with diabetes mellitus type 2 who can give written consent will be eligible for enrollment. They must meet all criteria.
• \> 21 years of age
• Body mass index (BMI) ≥30 kg/m2
• On insulin at least 2 times daily comprising both a basal and a prandial insulin or a pre-mix insulin with or without other non-insulin medications for a least past 3 months
• A1c \>8%
• eGFR \>45%

You may not qualify if:

• The patients with any of the following criteria will be excluded.
• Pregnancy
• Patients who are on a SGLT2i and a GLP1 RA injection at the time of enrollment.
• diabetes mellitus type 1
• C-peptide below normal range if measured in the past.
• patients with a history of diabetes ketoacidosis
• A history of recent and frequent (≥ 2 times within past 3 months) urinary tract infection or genito-urinary candidiasis requiring antibiotic and/or anti-fungal therapies.
• a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• eGFR \<45%
• patients with a history of acute pancreatitis

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Fresno

Fresno, California, 93701, United States

Location

Related Publications (3)

• Herman WH, Kalyani RR, Wexler DJ, Matthews DR, Inzucchi SE. Response to Comment on American Diabetes Association. Approaches to Glycemic Treatment. Sec. 7. In Standards of Medical Care in Diabetes-2016. Diabetes Care 2016;39(Suppl. 1):S52-S59. Diabetes Care. 2016 Jun;39(6):e88-9. doi: 10.2337/dci16-0003. No abstract available.

  PMID: 27222560 BACKGROUND

• Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Henry RR, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE; American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE). CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. Endocr Pract. 2016 Jan;22(1):84-113. doi: 10.4158/EP151126.CS. No abstract available.

  PMID: 26731084 BACKGROUND

• Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.

  PMID: 25011946 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rGLP-1 protein; dulaglutide; Insulin Glargine; Insulin Detemir; Sodium-Glucose Transporter 2 Inhibitors; empagliflozin; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: SOE NAING
• Organization: University of California San Francisco, Fresno Medical Education Program

snaing@fresno.ucsf.edu

5593239236

Study Officials

• SOE NAING, MD

  UCSF - Fresno

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 27, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: November 10, 2020
• Results First Posted: November 10, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)