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Waugh N, Cummins E, Royle P, et al. Newer Agents for Blood Glucose Control in Type 2 Diabetes (Supplement) [Internet]. London: National Institute for Health and Clinical Excellence (UK); 2009 May. (NICE Clinical Guidelines, No. 87S.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Newer Agents for Blood Glucose Control in Type 2 Diabetes (Supplement) [Internet].

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Appendix 3Characteristics of included trials – DPP-4 inhibitors

StudyMethodsParticipantsInterventionsOutcomes
Bolli 2008TRIAL DESIGN: RCT
DURATION OF INTERVENTION: 24 weeks
DURATION OF FOLLOW- UP: 24 weeks
RUN-IN PERIOD: None reported
RANDOMISATION PROCEDURE: Not reported
BLINDING: Reported as ‘double-blind’
SETTING: Not clear
COUNTRY: Multinational – Germany, UK, USA, Spain, Italy, Switzerland, Austria, South Africa, Australia
ITT ANALYSIS? No, per- protocol analysis
DESCRIPTION OF WITHDRAWALS AND LOSSES TO FOLLOW-UP: Adequate
SAMPLE SIZE CALCULATION: Yes, and adequately powered per- protocol
OVERALL RISK OF BIAS: +
SOURCE OF FUNDING: Novartis
WHO PARTICIPATED: Patients with type 2 diabetes inadequately controlled with prior metformin monotherapy
INCLUSION CRITERIA: 18 to 77 years of age, type 2 diabetes, treated with metformin ≥1500mg per day, screening HbA1 7.5–11.0%, non-fertile or using a medically approved birth control method, BMI 22 to 45kg/m2, FPG<15mmol/l
EXISTING THERAPY: failing metformin
EXCLUSION CRITERIA: History of type 1 diabetes or secondary forms of diabetes, acute metabolic diabetic complications. myocardial infarction. unstable angina or coronary artery bypass surgery within the previous 6 months, congestive heart failure (NYHA I–IV) and liver disease such as cirrhosis or chronic active hepatitis. Also specific abnormal lab.
NUMBERS: 576 randomised
AGE: Vilda100mg+met 56.3 years SD 9.3 and pio30mg+met 57.0 years SD 9.7
DURATION OF DIABETES: Vilda100mg+met 6.4 years SD 4.9 and pio30mg+met 6.4 years SD 5.2
HbA1c: Vilda100mg+met 8.4% SD 1.0 and pio30mg+met 8.4% SD 0.9
GENDER: Vilda100mg+met 61.7% males and pio30mg+met 64.1% males
ETHNIC GROUPS: Vilda100mg+met white 82.4%, hispanic or latino 8.5% asian (non-indian subcontinent) 4.1% black 3.0% others 2.0% pio30mg+met white 81.9%, hispanic or latino 10.3% asian (non-indian subcontinent) 3.9% black 2.5% others 1.4%
COMORBIDITIES: not reported
COMEDICATIONS: not reported
INTERVENTION: vildagliptin 100mg daily, two equally divided doses
CONTROL: pioglitazone 30mg once daily
OTHER TREATMENT: Assumed that participants continued current regimen of metformin.
PRIMARY OUTCOMES:
  1. HbA1c
    *mean HbA1c change from baseline
  2. Percentage of patients responsive to treatment (HbA1c<7%, ≤6.5%, reduction ≥1%, ≥0.7%, ≥0.5%, meeting at least one criteria)
SECONDARY OUTCOMES:
  1. Fasting lipids
  2. Body weight
    *Change in body weight (kg) from baseline to 24 weeks
Safety
Hermansen 2007TRIAL DESIGN: RCT
DURATION OF INTERVENTION: 24 weeks
DURATION OF FOLLOW- UP: 24 weeks
RUN-IN PERIOD: upto 14 weeks
RANDOMISATION PROCEDURE: Not reported but 1:1
BLINDING: Reported a s ‘double-blind’
SETTING: Not clear
COUNTRY: reported as ‘multinational’
ITT ANALYSIS? Yes, with LOCF
DESCRIPTION OF WITHDRAWALS AND LOSSES TO FOLLOW-UP: Adequate
SAMPLE SIZE CALCULATION: Yes, but not reported if numbers achieved
OVERALL RISK OF BIAS: +
SOURCE OF FUNDING: Merck
WHO PARTICIPATED: Patients with type 2 diabetes
INCLUSION CRITERIA: 18 to 75 years of age, type 2 diabetes, taking either glimepiride (any dose) alone or in combination with metformin (any dose), or taking another oral hypoglycaemic drug mono-dual-or triple therapy or not taking any oral hypoglycaemic drug during the previous 8 weeks
EXISTING THERAPY: If taking glimepiride alone or with metformin, entered placebo run-in. If other regime and depending on HbA1c control, discontinued and started treatment with glimepiride alone or with metformin, dose titrated for 4 weeks, then run-in period 10 weeks, with placebo run-in period if HbA1c ≥7.5% and ≤ 10.5%. Entered for randomization if adherence ≥75%
EXCLUSION CRITERIA: History of type 1 diabetes, treated with insulin in prior 8 weeks, renal dysfunction, history of hypersensitivity, intolerance or contraindications to glimepiride, sulphonylureas, metformin or pioglitazone.
NUMBERS: 441 randomised - sit100mg+MET+SU 116 placebo+MET+SU 113
AGE: sit100mg+MET+SU 56.5 years SD 9.6 and placebo+MET+SU 57.7 years SD 8.9
DURATION OF DIABETES: sit100mg+MET+SU 9.3 years SD 5.7 and placebo+MET+SU 10.6 years SD 6.8
HbA1c: sit100mg+MET+SU 8.27% SD 0.73 and placebo+MET+SU 8.26% SD 0.68
GENDER: sit100mg+MET+SU 52.6% males and placebo+MET+SU 59% males
ETHNIC GROUPS: sit100mg+MET+SU white 64.7%, black 6.6% hispanic 24.5% asian 5.7% others 5.7% placebo+MET+SU white 71.7%, black 8.0% hispanic 6.2% asian 11.5% others 2.7%
COMORBIDITIES: not reported
COMEDICATIONS: not reported
INTERVENTION: sitagliptin 100mg once daily
CONTROL: placebo
OTHER TREATMENT: Continued stable doses of glimepiride and metformin (as established in the run-in period). Also given rescue therapy of pioglitazone 30mg/day (open label) if FPG not meeting specific, and progressively lower goals after randomization. Discontinued from study if rescue therapy for more than 4 weeks and FPG still high.

NOTE: Only reported details for relevant comparator arms
PRIMARY OUTCOMES:
  1. HbA1c
    *mean HbA1c change from baseline. If significant then assessed treatment effects by strata
SECONDARY OUTCOMES:
  1. Fasting lipids – TC, LDL- C, TG, HDL-C
  2. Beta cell function
  3. Changes in insulin resistance
Safety and tolerability
Nauck 2007TRIAL DESIGN: RCT
DURATION OF INTERVENTION: 52 weeks
DURATION OF FOLLOW- UP: 52 weeks
RUN-IN PERIOD: 2 week single-blind PLACEBO
RANDOMISATION PROCEDURE: Not reported, 1:1 ratio
BLINDING: Double blinded. Except for lead-in period (single blind)
SETTING: Not clear
COUNTRY: Described as ‘multinational’
ITT ANALYSIS? Per- protocol and all-patients treated analysis
DESCRIPTION OF WITHDRAWALS AND LOSSES TO FOLLOW-UP: Adequate
SAMPLE SIZE CALCULATION: Not reported
OVERALL RISK OF BIAS: -
SOURCE OF FUNDING: Merck
WHO PARTICIPATED: Patients with type 2 with inadequate control on metformin
INCLUSION CRITERIA: 18– 78 years of age, type 2 diabetes, treated with metformin (eligible if not taking any oral therapy, any oral therapy as monotherapy, any oral therapy with metformin, then titrated to
METFORMIN monotherapy over 8 week period)
EXISTING THERAPY: failing metformin
EXCLUSION CRITERIA: History of type 1 diabetes, insulin use within 8 weeks of screening, renal function impairment inconsistent with use of metformin, FPG at or prior to randomization>15.0mmol/l
NUMBERS: 1172 randomised
AGE: SIT+MET 56.8 (SD9.3) and SU+MET 56.6 (SD9.8) years
DURATION OF DIABETES: SIT+MET 6.5 years (SD6.1) and SU+MET 6.2years (SD5.4)
HbA1c: SIT+MET 7.7 (SD0.9)and SU+MET 7.6 (SD0.9)
GENDER: SIT+MET 57.1% males SU+MET 61.3%
ETHNIC GROUPS: SIT+MET white 73.5%, black 7.0%, hispanic 7.3%, asian 8.5%, other 3.7% SU+MET white 74.3%, black 6.0%, hispanic 739%, asian 8.4%, other 3.4%
COMORBIDITIES: Not reported
COMEDICATIONS: Allowed lipid lowering, antihypertensive, thyroid, medications and HRT, birth control – but expected to remain at stable doses. Other treatments for hyperglycaemia not allowed.
PHARMACONAIIVE: SIT+MET 4.3% and SU+MET 4.8% at screening
INTERVENTION: sitagliptin 100mg once daily
CONTROL: glipizide, initial dose of 5mg with uptitration according to protocol specifications to max of 20mg/day
OTHER TREATMENT: Assumed that all participants continued stable regimen of metformin.
PRIMARY OUTCOMES:
  1. HbA1c
    *mean HbA1c change from baseline
SECONDARY OUTCOMES:
  1. HbA1c
    *Number (%) of patients achieving HbA1c equal to or less than 7% or 6.5% Change in HbA1c stratified by baseline A1c
Safety and tolerability Adverse experiences, lab safety parameters, body weight, vital signs, ECG data Compliance
tablet count
Scott 2007TRIAL DESIGN: RCT
DURATION OF INTERVENTION: 18 weeks
DURATION OF FOLLOW- UP: 18 weeks
RUN-IN PERIOD: 2 week single-blind PLACEBO
RANDOMISATION PROCEDURE: Not reported, 1:1:1 ratio
BLINDING: Double blinded. Except for lead-in period (single blind)
SETTING: Not clear
COUNTRY: Described as ‘multinational’
ITT ANALYSIS? All patients treated analysis
DESCRIPTION OF WITHDRAWALS AND LOSSES TO FOLLOW-UP: Adequate
SAMPLE SIZE CALCULATION: Not reported
OVERALL RISK OF BIAS: +
SOURCE OF FUNDING: Merck
WHO PARTICIPATED: Patients with type 2 diabetes treated with metformin
INCLUSION CRITERIA: 18 to 75 years of age, type 2 diabetes, treated with metformin at stable dose of at least 1500mg/day for at least 10 weeks prior to screening, HbA1c 7 to 11%
EXISTING THERAPY: failing metformin
EXCLUSION CRITERIA: Type 1 diabetes, insulin use within 8 weeks of screening, impaired renal function, contraindications for TZDs or metformin.
NUMBERS: 273 randomised
AGE: SIT100 55.2 years SD 9.8 and ROSI8 54.8 years SD 10.5 and PLACEBO 55.3 years SD 9.3
DURATION OF DIABETES: SIT100 4.9 years SD 3.5 and ROSI8 4.6 years SD 4.0 and PLACEBO 5.4 years SD 3.7
HbA1c: SIT100 7.8 SD 1.0 and ROSI8 737 SD 0.8 and PLACEBO 7.7 SD 0.9
GENDER: SIT100 55% males ROSI8 63% males and PLACEBO 59% males
ETHNIC GROUPS: SIT100 caucasian 61%, asian 38%, others 1% ROSI8 caucasian 59%, asian 38%, others 3% PLACEBO caucasian 61%, asian 39%, others 0%
COMORBIDITIES: 59% hypertension, 42% hyperlididaemia/dyslipidaemia
COMEDICATIONS: Not reported
PHARMACONAIIVE:N/A
INTERVENTION: sitagliptin 100mg once daily
INTERVENTION: rosiglitazone 8,g once daily
CONTROL: Placebo once daily
OTHER TREATMENT: All participants continued current regimen of metformin. All patients received counseling on exercise and a weight maintaining diet
PRIMARY OUTCOMES:
  1. HbA1c
    *mean HbA1c change from baseline
  2. Beta-cell function Proinsulin/insulin ratio and HOMA-beta
  3. Meal tolerance test
SECONDARY OUTCOMES:
  1. Adverse experiences
  2. Physical examinations
  3. Vital signs
  4. Body weight
Copyright © 2009, National Institute for Health and Clinical Excellence.

All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of NICE.

Bookshelf ID: NBK61933

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