Efficacy and safety of antihyperglycaemic drug regimens added to metformin and sulphonylurea therapy in Type 2 diabetes: a network meta‐analysis

Mearns, Elizabeth S.; Saulsberry, Whitney J; White, C Michael; Kohn, Christine G.; Lemieux, Simone; Sihabout, A.; Salamucha, I.; Coleman, Craig I.

doi:10.1111/dme.12837

Cited by 45 publications

(37 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the mouse is hyperinsulinemic at an early age with impaired glucose disposal and elevated triglycerides when compared to normal mice. The obese, insulin resistant FATZO mouse responded to the three classes of anti-diabetic agents described above in a fashion comparable to that of humans and other obese models of type 2 diabetes [89–91]. Body weight reduction with improved glucose tolerance was observed in obese FATZO mice treated with metformin (150 mg/kg/day) and an improvement in glucose tolerance with significant weight gain followed rosiglitazone (10 mg/kg/day) treatment.…”

Section: Discussionmentioning

confidence: 97%

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

Peterson¹,

Jackson²,

Zimmerman³

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Conclusion: Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents.

show abstract

Section: Discussionmentioning

confidence: 97%

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

Peterson¹,

Jackson²,

Zimmerman³

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…We also assumed that patients’ medications would change in the year after their HbA 1c value increased above (or decreased >1% below) their goal and that each medication reduced the HbA 1c level by 1% (21–23). Under the individualized strategy, as patients developed complications and aged, their goals increased (for example, from an HbA 1c level <6.5% to a level <7.0% to a level <8.0%).…”

Section: Methodsmentioning

confidence: 99%

Individualized Glycemic Control for U.S. Adults With Type 2 Diabetes

et al. 2017

View full text Add to dashboard Cite

Background Intensive glycemic control in type 2 diabetes (glycated hemoglobin [HbA1c] level <7%) is an established, cost-effective standard of care. However, guidelines recommend individualizing goals on the basis of age, comorbidity, diabetes duration, and complications. Objective To estimate the cost-effectiveness of individualized control versus uniform intensive control (HbA1c level <7%) for the U.S. population with type 2 diabetes. Design Patient-level Monte Carlo–based Markov model. Data Sources National Health and Nutrition Examination Survey 2011–2012. Target Population The approximately 17.3 million persons in the United States with diabetes diagnosed at age 30 years or older. Time Horizon Lifetime. Perspective Health care sector. Intervention Individualized versus uniform intensive glycemic control. Outcome Measures Average lifetime costs, life-years, and quality-adjusted life-years (QALYs). Results of Base-Case Analysis Individualized control saved $13 547 per patient compared with uniform intensive control ($105 307 vs. $118 854), primarily due to lower medication costs ($34 521 vs. $48 763). Individualized control decreased life expectancy (20.63 vs. 20.73 years) due to an increase in complications but produced more QALYs (16.68 vs. 16.58) due to fewer hypoglycemic events and fewer medications. Results of Sensitivity Analysis Individualized control was cost-saving and generated more QALYs compared with uniform intensive control, except in analyses where the disutility associated with receiving diabetes medications was decreased by at least 60%. Limitation The model did not account for effects of early versus later intensive glycemic control. Conclusion Health policies and clinical programs that encourage an individualized approach to glycemic control for U.S. adults with type 2 diabetes reduce costs and increase quality of life compared with uniform intensive control. Additional research is needed to confirm the risks and benefits of this strategy. Primary Funding Source National Institute of Diabetes and Digestive and Kidney Diseases.

show abstract

“…Because the NMA is a decision-focused approach that concentrates on a comparison of alternative DPP-4 inhibitors in triple therapy, the studies selected are more homogeneous than other broader NMAs in triple therapy that have previously been reported [13, 14, 39], and a relatively narrow network will reduce heterogeneity and noise that might be seen with larger networks. The lack of studies preventing running NMA random effects models at the individual DPP-4 treatment level has to be acknowledged as a limitation.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Adding Alogliptin to Metformin Plus Sulfonylurea with Other DPP-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

Kay

Strickson²,

Puelles

et al. 2017

Diabetes Ther

View full text Add to dashboard Cite

IntroductionAlogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy.MethodsA systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated.ResultsThe review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy.ConclusionThis decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708).Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0245-8) contains supplementary material, which is available to authorized users.

show abstract

Efficacy and safety of antihyperglycaemic drug regimens added to metformin and sulphonylurea therapy in Type 2 diabetes: a network meta‐analysis

Abstract: When added to metformin and a sulphonylurea, antihyperglycaemic agents had varying effects on efficacy and safety endpoints. These conclusions should be considered when clinicians choose between possible adjunctive agents.

Cited by 45 publications

References 36 publications

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

Individualized Glycemic Control for U.S. Adults With Type 2 Diabetes

Comparative Effectiveness of Adding Alogliptin to Metformin Plus Sulfonylurea with Other DPP-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

Contact Info

Product

Resources

About