Relationship of Baseline HbA<sub>1c</sub>
 and Efficacy of Current Glucose Lowering Therapies: A Meta-Analysis of Randomised Clinical Trials

DeFronzo, R. A.; Stonehouse, Anthony H.; Han, J.; Wintle, M. E.

doi:10.1111/j.1464-5491.2009.02941.x

Cited by 64 publications

(86 citation statements)

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“…This is because there is a greater potential for improvement in glycemic control in patients with higher baseline HbA1c. Similar relationships between baseline HbA1c levels and improvements in glycemic control have also been seen in previous reports of meta-analyses of various glucose-lowering therapies [13], meta-analyses of GLP-1 receptor agonists other than dulaglutide [14,15], and global phase 3 studies of dulaglutide [16].…”

Section: Discussionsupporting

confidence: 58%

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

et al. 2017

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Section: Discussionsupporting

confidence: 58%

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

et al. 2017

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“…The coefficient β(HbA1c) for the HbA1c endpoint was found to be significant for the 24-week fixed-effect NMA and borderline significant for the 24-week random-effects NMA. This is consistent with clinical observations that suggest there is a trend towards a larger reduction in HbA1c given a higher HbA1c at baseline [19]. The other coefficients (weight and age) in the 24-week analysis were not found to be significant.…”

Section: Strengths and Limitationssupporting

confidence: 89%

“…To maximise the data, missing baseline values were calculated assuming observed and unobserved values were exchangeable [18]. Previous meta-analyses have shown that there is a correlation between the average baseline HbA1c and change in HbA1c over follow-up [19] and it is known that glycaemic control is harder to achieve in overweight or obese patients [20]. Patient age was also considered to be a potential effect modifier in itself.…”

Section: Meta-analysesmentioning

confidence: 99%

Systematic Review and Network Meta-analysis to Compare Dapagliflozin with other Diabetes Medications in Combination with Metformin for Adults with Type 2 Diabetes

Barnett

Me²,

Fenici³

et al. 2014

Intern Med

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Objective: A network meta-analysis (NMA) update was undertaken to evaluate the sodium glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, versus other antidiabetes medications as add-on to metformin. This update allowed inclusion of a new drug class (glucagon-like peptide-1 [GLP-1] analogues), a new time point (24-weeks) and covariate analysis. Methods:The systematic review identified randomised controlled trials involving patients with type-2 diabetes mellitus (T2DM) inadequately controlled on metformin. Comparators included dipeptidyl peptidase-4 inhibitors (DPP-4i), thiazolidinediones (TZDs), GLP-1s, sulfonylureas (SUs) and dapagliflozin. Bayesian NMA was conducted at 24-and 52-weeks for mean change in HbA1c, systolic blood pressure (SBP), weight, and proportion of patients experiencing hypoglycaemia. Results:The systematic review identified 2247 articles, of which 16were eligible for inclusion. Combined with 19 studies frompre-2011 analysis, a total of 19 and 8 studies were included in the 24-week and 52-week NMA, respectively. There were no significant differences in HbA1c or SBP between dapagliflozin and other classes, including GLP-1s, at either time point. Significant results were seen for weight loss by 24-weeks for dapagliflozin versusDPP-4i (-2.24 kg [95% CI -3.25,-1.24]) and TZDs (-4.65 kg [-5.89,-3.45]), and at 52-weeks versus SUs, DPP-4i and TZDs. Dapagliflozin also resulted in significantly lower hypoglycaemia risk versus SU (OR: 0.05 [0.01,0.19]) over 52-weeks. Conclusions:This NMA update supports previous findings that effects on HbA1c are similar between drug classes and that dapagliflozin plus metformin offers superior weight control for T2DM patients compared with many other agents. The wider evidence base compared to previous analysis increases the confidence in the results.

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“…Meta-analyses of large clinical trials have demonstrated a positive correlation between baseline HbA 1c and the magnitude of HbA 1c response to therapy, independent of drug class or mechanism of action [122,123]. Consistent with these reports, ExBID-treated patients with a high mean baseline HbA 1c of 10.2% had a mean HbA 1c change of -1.74% after 24 weeks of treatment [86].…”

Section: Overviewmentioning

confidence: 68%

Evolution of Exenatide as a Diabetes Therapeutic

Bhavsar¹,

Mudaliar²,

Cherrington³

2013

Current Diabetes Reviews

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Type 2 diabetes (T2DM) is a disease of epidemic proportion associated with significant morbidity and excess mortality. Optimal glucose control reduces the risk of microvascular and possibly macrovascular complications due to diabetes. However, glycemic control is rarely optimal and several therapeutic interventions for the treatment of diabetes cause hypoglycemia and weight gain; some may exacerbate cardiovascular risk. Exenatide (synthetic exendin-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist developed as a first-in-class diabetes therapy. This review presents an overview of the evolution of exenatide as a T2DM treatment, beginning with the seminal preclinical discoveries and continuing through to clinical pharmacology investigations and phase 3 clinical trials. In patients with T2DM, exenatide enhanced glucose-dependent insulin secretion, suppressed inappropriately elevated glucagon secretion, slowed gastric emptying, and enhanced satiety. In controlled phase 3 clinical trials ranging from 12 to 52 weeks, 10-mcg exenatide twice daily (ExBID) reduced mean HbA 1c by -0.8% to -1.7% as monotherapy or in combination with metformin (MET), sulfonylureas (SFU), and/or thiazolidinediones (TZD); with mean weight losses of -1.2 kg to -8.0 kg. In controlled phase 3 trials ranging from 24 to 30 weeks, a 2-mg once-weekly exenatide formulation (ExQW) reduced mean HbA 1c by -1.3% to -1.9%, with mean weight reductions of -2.3 to -3.7 kg. Exenatide was generally well-tolerated. The most common side effects were gastrointestinal in nature, mild, and transient. Nausea was the most prevalent adverse event. The incidence of hypoglycemia was generally low. By building upon early observations exenatide was successfully developed into an effective diabetes therapy.

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Relationship of Baseline HbA_1c and Efficacy of Current Glucose Lowering Therapies: A Meta-Analysis of Randomised Clinical Trials

Cited by 64 publications

References 0 publications

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

Systematic Review and Network Meta-analysis to Compare Dapagliflozin with other Diabetes Medications in Combination with Metformin for Adults with Type 2 Diabetes

Evolution of Exenatide as a Diabetes Therapeutic

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Relationship of Baseline HbA1c and Efficacy of Current Glucose Lowering Therapies: A Meta-Analysis of Randomised Clinical Trials

Cited by 64 publications

References 0 publications

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

Systematic Review and Network Meta-analysis to Compare Dapagliflozin with other Diabetes Medications in Combination with Metformin for Adults with Type 2 Diabetes

Evolution of Exenatide as a Diabetes Therapeutic

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Resources

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Relationship of Baseline HbA_1c and Efficacy of Current Glucose Lowering Therapies: A Meta-Analysis of Randomised Clinical Trials