Efficacy and tolerability of exenatide twice daily and exenatide once weekly in Asian versus White patients with type 2 diabetes mellitus: A pooled analysis

Sheu, Wayne Huey‐Herng; Brunell, Steven C.; Blase, Erich

doi:10.1016/j.diabres.2015.12.004

Cited by 19 publications

(27 citation statements)

References 43 publications

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“…Previous studies in the same database suggested Asian participants with T2D respond to exenatide twice daily better than white participants . This analysis extends these findings by showing this effect is independent of baseline HbA1c.…”

Section: Discussionsupporting

confidence: 80%

Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly

Shaw

Gallwitz

Han

et al. 2017

Diabetes Obesity Metabolism

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The range of glycated haemoglobin (HbA1c) responses and characteristics associated with above‐average response to exenatide twice daily and once weekly were examined. Data were pooled from 8 exenatide‐twice‐daily and 5 exenatide‐once‐weekly studies. A baseline HbA1c‐corrected measure of change in HbA1c after 24 weeks identified high, average and low responses. Multiple linear regression and multivariate generalized estimating equation models identified factors associated with high response. Among 2355 participants (exenatide twice daily, n = 1414; exenatide once weekly, n = 941), baseline HbA1c correlated with change in HbA1c (P < .0001). Across baseline HbA1c levels, the 25th to 75th percentile of HbA1c change ranged from −0.3% to −3.2% with exenatide twice daily and from −0.5% to −3.6% with exenatide once weekly. Asian ethnicity and older age were significantly associated with high response to exenatide twice daily; no factors were significantly associated with response to exenatide once weekly. These data provide clinically useful information for estimating the likelihood that, depending on baseline HbA1c, an individual can achieve HbA1c goals. The association between Asian ethnicity, age and high response to exenatide twice daily may relate to the specific effects of exenatide twice daily on postprandial glucose.

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Section: Discussionsupporting

confidence: 80%

Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly

Shaw

Gallwitz

Han

et al. 2017

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…In a study investigating exenatide twice daily and once weekly, HbA1c reductions with exenatide twice daily were greater among Asian patients vs white patients ( P < .0001), but weight loss was greater among white patients . There was no effect of race on HbA1c reduction with exenatide once weekly in this study, although white patients lost more weight than Asian patients with exenatide once weekly . A pooled analysis of the effect of exenatide once weekly according to age, sex, race, T2DM duration, and BMI showed no differences in HbA1c and body weight reductions in any of the subpopulations investigated .…”

Section: Discussioncontrasting

confidence: 48%

“…Analyses of exenatide twice daily treatment have shown that reductions in HbA1c and body weight are generally unaffected by baseline HbA1c or baseline BMI; however, one study found that patients with a T2DM duration of >15 years lost more weight with exenatide twice daily vs placebo than patients with a shorter disease duration . In a study investigating exenatide twice daily and once weekly, HbA1c reductions with exenatide twice daily were greater among Asian patients vs white patients ( P < .0001), but weight loss was greater among white patients . There was no effect of race on HbA1c reduction with exenatide once weekly in this study, although white patients lost more weight than Asian patients with exenatide once weekly .…”

Section: Discussionmentioning

confidence: 96%

Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone, or dapagliflozin alone added to metformin monotherapy in subgroups of patients with type 2 diabetes in the DURATION‐8 randomized controlled trial

Frías

Hardy

Ahmed³

et al. 2018

Diabetes Obesity Metabolism

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This analysis assessed whether responses with exenatide once weekly plus dapagliflozin (n = 231), exenatide once weekly alone (n = 230), or dapagliflozin alone (n = 233) differed in key patient subpopulations of the DURATION‐8 trial. Potential treatment‐by‐subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28 weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all subgroups: least‐squares mean reductions ranged from −8.4 to −26.1 mmol/mol (−0.77% to −2.39%) for HbA1c and from −2.07 to −4.55 kg for body weight. Potential treatment‐by‐subgroup interactions (P < .10) were found for HbA1c change by age (P = .016) and eGFR (P = .097). Age subgroup analysis findings were not consistent with expected mechanistic effects, with the small number of patients aged ≥65 years (n = 74 vs n = 499 for patients aged <65 years) limiting the interpretability of the interaction term. In the exenatide once weekly plus dapagliflozin and dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions were greater among patients with eGFR ≥90 vs ≥60 to <90 mL/min/1.73 m2 (least‐squares mean reductions of −23.6 vs −19.0 mmol/mol [−2.16% vs −1.74%], −17.3 vs −12.0 mmol/mol [−1.58% vs −1.10%], and −17.7 vs −16.9 mmol/mol [−1.62% vs −1.55%] for the respective treatments); this was consistent with the mechanism of action of dapagliflozin. A potential treatment‐by‐subgroup interaction was observed for change in body weight by sex (P = .099), with greater weight loss for women vs men across all treatments (range −2.56 to −3.98 kg vs −0.56 to −2.99 kg). In conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all patient subgroups and was more effective than exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.

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“…Currently, four such drugs available in the United States: exendin-4 or its synthetic version exenatide, liraglutide, albiglutide, and dulaglutide. Various products are in different stages of research and development (2, 6–8). The effectiveness of these drugs has led to increasing interest in the mechanisms underlying their effects on bone metabolism.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

et al. 2017

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The impact of antidiabetic drugs on bone metabolism is drawing increasing attention due to the discovery of a correlation between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel and promising class of drugs for T2DM, which may also have clinical applications in bone tissue disorders. This review examines the impact of GLP-1 on bone metabolism, including enhancement of bone mineral density and improvement of bone quality. However, the precise effect of GLP-1 on fracture risk has not been unambiguously defined. This review also summarizes our current understanding of the mechanisms by which GLP-1 affects bone metabolism. GLP-1 may act on bone by promoting bone formation, inhibiting bone resorption, and affecting the coordination of the two processes. We describe molecular pathways and proteins, such as Wnt and calcitonin, that are associated with GLP-1 and bone tissue. The specific processes and related molecular mechanisms of the effects of GLP-1 on bone metabolism need to be further explored and clarified.

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Efficacy and tolerability of exenatide twice daily and exenatide once weekly in Asian versus White patients with type 2 diabetes mellitus: A pooled analysis

Abstract: Exenatide BID and QW improved glycemic control, including PPG, in Asian and White patients with T2DM. With exenatide BID, Asian patients exhibited significantly greater reductions in HbA1c and PPG than White patients. Both exenatide formulations were well tolerated in both groups.

Cited by 19 publications

References 43 publications

Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly

Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly

Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone, or dapagliflozin alone added to metformin monotherapy in subgroups of patients with type 2 diabetes in the DURATION‐8 randomized controlled trial

The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

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