Effect of Linagliptin + Metformin vs Metformin Alone in Patients With Prediabetes

NCT03004612 | Completed Phase 4 DMC

• 1 other identifier: CEI-22-16
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes is a worldwide epidemic disease, and preventive strategies are needed to face this health problem. The goal of this clinical trial is to evaluate the effect of linagliptin + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism, insulin resistance, insulin secretion and pancreatic beta cell function in patients with impaired fasting glucose plus impaired glucose tolerance, during 24 months.

Conditions

Prediabetic State; Insulin Resistance

Keywords

prediabetes

Outcome Measures

Primary Outcomes (1)

• Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months

  Fasting and post-2h OGTT glucose values (mg/dl)

  12 and 24 months

Secondary Outcomes (4)

• Change from basal pancreatic beta cell function at 12 and 24 months

  12 and 24 months

• Change from basal insulin sensitivity at 12 and 24 months

  12 and 24 months

• Change from basal Weight at 12 and 24 months

  12 and 24 months

• Incidence of type 2 diabetes

  24 months

Study Arms (2)

Linagliptin + Metformin plus lifestyle

EXPERIMENTAL

Patients are randomized to receive for 24 months Linagliptin 2.5mg + metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.

Combination Product: Linagliptin + metformin

Metformin plus lifestyle

ACTIVE COMPARATOR

Patients are randomized to receive for 24 months Metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.

Drug: Metformin

Interventions

Linagliptin + metformin COMBINATION_PRODUCT

Linagliptin-Metformin 2.5/850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Also known as: Tradjenta Duo

Linagliptin + Metformin plus lifestyle

Metformin DRUG

Metformin 850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Metformin plus lifestyle

Eligibility Criteria

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

You may qualify if:

• Patients with prediabetes, defined for the existence impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT) ) with or without impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL)
• Patients who accept to participate in the study and sign the informed consent letter.

You may not qualify if:

• Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the OGTT
• Patients in actual treatment or during the last 3 months with metformin, pioglitazone or another antidiabetic drug, including insulin.
• Serum creatinine \> 1.6 mg/dL
• Hypertriglyceridemia very high (\>500 mg/dL)
• Pregnant women
• Altered arterial hypertension (Systolic \> 180 mmHg or Diastolic \>105 mmHg)
• Excessive alcohol intake, acute or chronic
• Medications or medical conditions that affect glucose homeostasis (thiazides, beta blockers, glucocorticoids for systemic use, weight-reducing drugs or anorexigenics, Cushing's syndrome, Thyrotoxicosis.

Sponsors & Collaborators

• Universidad de Guanajuato: lead
• Hospital Regional de Alta Especialidad del Bajio: collaborator

Study Sites (1)

Universidad de Guanajuato

León, Guanajuato, 37670, Mexico

Location

Related Publications (14)

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  PMID: 9727886 BACKGROUND

• Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.

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• Faerch K, Vaag A, Holst JJ, Glumer C, Pedersen O, Borch-Johnsen K. Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action. Diabetologia. 2008 May;51(5):853-61. doi: 10.1007/s00125-008-0951-x. Epub 2008 Mar 4.

  PMID: 18317726 BACKGROUND

• Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care. 2009 Mar;32(3):439-44. doi: 10.2337/dc08-1195. Epub 2008 Dec 3.

  PMID: 19056613 BACKGROUND

• Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr;20(4):537-44. doi: 10.2337/diacare.20.4.537.

  PMID: 9096977 BACKGROUND

• Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.

  PMID: 11333990 BACKGROUND

• Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.

  PMID: 11832527 BACKGROUND

• Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002 Jun 15;359(9323):2072-7. doi: 10.1016/S0140-6736(02)08905-5.

  PMID: 12086760 BACKGROUND

• Drucker DJ, Sherman SI, Gorelick FS, Bergenstal RM, Sherwin RS, Buse JB. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care. 2010 Feb;33(2):428-33. doi: 10.2337/dc09-1499. No abstract available.

  PMID: 20103558 BACKGROUND

• Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, Trautmann M. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010 Jun;33(6):1173-5. doi: 10.2337/dc09-1203. Epub 2010 Mar 23.

  PMID: 20332357 BACKGROUND

• Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Reaven G. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014 Mar;57(3):455-62. doi: 10.1007/s00125-013-3134-3. Epub 2013 Dec 11.

  PMID: 24326527 BACKGROUND

• Heise T, Graefe-Mody EU, Huttner S, Ring A, Trommeshauser D, Dugi KA. Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab. 2009 Aug;11(8):786-94. doi: 10.1111/j.1463-1326.2009.01046.x. Epub 2009 May 19.

  PMID: 19476474 BACKGROUND

• Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther. 2014 Jun;5(1):1-41. doi: 10.1007/s13300-014-0061-3. Epub 2014 Mar 25.

  PMID: 24664619 BACKGROUND

• Del Prato S, Taskinen MR, Owens DR, von Eynatten M, Emser A, Gong Y, Chiavetta S, Patel S, Woerle HJ. Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: pooled analysis of data from three placebo-controlled phase III trials. J Diabetes Complications. 2013 May-Jun;27(3):274-9. doi: 10.1016/j.jdiacomp.2012.11.008. Epub 2013 Feb 9.

  PMID: 23403068 BACKGROUND

MeSH Terms

Conditions

Prediabetic State; Insulin Resistance

Interventions

Linagliptin; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Rodolfo Guardado-Mendoza, MDPhD

  Universidad de Guanajuato

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MDPhD

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: December 29, 2016
• Study Start: January 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 9, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)