Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data

The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects dif...

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Veröffentlicht in:Diabetes care Jg. 41; H. 9; S. 1844
Hauptverfasser: Dennis, John M, Henley, William E, Weedon, Michael N, Lonergan, Mike, Rodgers, Lauren R, Jones, Angus G, Hamilton, William T, Sattar, Naveed, Janmohamed, Salim, Holman, Rury R, Pearson, Ewan R, Shields, Beverley M, Hattersley, Andrew T
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.09.2018
Schlagworte:
Adult
Aged
Aged, 80 and over
Blood Glucose - drug effects
Blood Glucose - metabolism
Body Mass Index
Cost-Benefit Analysis
Datasets as Topic - statistics & numerical data
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - economics
Diabetes Mellitus, Type 2 - epidemiology
Female
Humans
Hypoglycemia - chemically induced
Hypoglycemia - economics
Hypoglycemia - epidemiology
Hypoglycemic Agents - economics
Hypoglycemic Agents - therapeutic use
Male
Metformin - economics
Metformin - therapeutic use
Middle Aged
Primary Health Care - statistics & numerical data
Randomized Controlled Trials as Topic - statistics & numerical data
Risk Assessment
Sex Factors
Sulfonylurea Compounds - economics
Sulfonylurea Compounds - therapeutic use
Thiazolidinediones - economics
Thiazolidinediones - therapeutic use
United Kingdom - epidemiology
ISSN:1935-5548, 1935-5548
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Zusammenfassung:The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones. We studied 22,379 patients starting sulfonylurea or thiazolidinedione therapy in the U.K. Clinical Practice Research Datalink (CPRD) to identify features associated with increased 1-year HbA fall with one therapy class and reduced fall with the second. We then assessed whether prespecified patient subgroups defined by the differential clinical factors showed differing 5-year glycemic response and side effects with sulfonylureas and thiazolidinediones using individual randomized trial data from ADOPT (A Diabetes Outcome Progression Trial) (first-line therapy, = 2,725) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) (second-line therapy, = 2,222). Further replication was conducted using routine clinical data from GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) ( = 1,977). In CPRD, male sex and lower BMI were associated with greater glycemic response with sulfonylureas and a lesser response with thiazolidinediones (both < 0.001). In ADOPT and RECORD, nonobese males had a greater overall HbA reduction with sulfonylureas than with thiazolidinediones ( < 0.001); in contrast, obese females had a greater HbA reduction with thiazolidinediones than with sulfonylureas ( < 0.001). Weight gain and edema risk with thiazolidinediones were greatest in obese females; however, hypoglycemia risk with sulfonylureas was similar across all subgroups. Patient subgroups defined by sex and BMI have different patterns of benefits and risks on thiazolidinedione and sulfonylurea therapy. Subgroup-specific estimates can inform discussion about the choice of therapy after metformin for an individual patient. Our approach using routine and shared trial data provides a framework for future stratification research in type 2 diabetes.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1935-5548
1935-5548
DOI:10.2337/dc18-0344