Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes

Desai, Urvi; Kirson, Noam Y.; Kim, Jennifer; Khunti, Kamlesh; King, Sarah; Trieschman, Erich; Hellstern, Michael; Hunt, Phillip R.; Mukherjee, Jayanti

doi:10.2337/dc17-0662

Cited by 41 publications

(45 citation statements)

References 26 publications

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“…Numerous studies have established that after treatment intensification, delays have been shown to be associated with poorer response to the added therapy. Thus, delaying treatment intensification exposes patients to avoidable hyperglycaemia both during and after the delays . These results highlight the benefit of early initiation of intensification therapy in patients not at target, and demonstrate that prolonged hyperglycaemia may be associated with decreased ability to reach target.…”

Section: Discussionmentioning

confidence: 77%

“…Thus, delaying treatment intensification exposes patients to avoidable hyperglycaemia both during and after the delays. [14][15][16][17] These results highlight the benefit of early initiation of intensification therapy in patients not at target, and demonstrate that prolonged hyperglycaemia may be associated with decreased ability to reach target.…”

Section: Discussionmentioning

confidence: 79%

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Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis

Raccah

Guerci

Ajmera

et al. 2019

Endocrino Diabet & Metabol

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Summary Aims To assess the effect of duration of hyperglycaemia before basal insulin (BI) initiation on clinical outcomes in type 2 diabetes (T2D). Materials and methods Patients with T2D who initiated BI during 2009‐2013, had continuous enrolment for ≥2 years preceding and ≥1 year following BI initiation (“index date”), and had ≥1 glycated haemoglobin (A1C) measure not at target (ie, ≥7.0%) within 6 months preindex date were included in the study. Patients were stratified by preindex‐date duration of A1C ≥7.0%. Longitudinal A1C, weight, BMI, and diabetes medication were compared between cohorts for up to 15‐month follow‐up. Results Of 37 053 patients who initiated BI, 40.7%, 15.3%, 16.0%, and 28.0%, respectively, had uncontrolled A1C for <6, 6‐<12, 12‐<18 and 18‐24 months preindex date. Baseline characteristics were similar between cohorts. Baseline A1C values were similar across cohorts (9.2%‐9.6%). Mean follow‐up A1C values were higher with longer preindex‐date duration of uncontrolled A1C (8.0 ± 1.7%, 8.2 ± 1.6%, 8.5 ± 1.7%, and 8.6 ± 1.7% for <6, 6‐<12, 12‐<18, and 18‐24 months); attainment of A1C <7.0% worsened with increasing preindex‐date duration of A1C ≥7.0% (29.6%, 20.0%, 14.6%, and 11.5% for <6, 6‐<12, 12‐<18, and 18‐24 months). Conclusions These data suggest that longer duration of uncontrolled A1C before BI initiation increases the risk of not reaching glycaemic targets. However, target attainment was poor in all cohorts, highlighting inadequate glycaemic control as an important unmet need in US patients with T2D.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 79%

Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis

Raccah

Guerci

Ajmera

et al. 2019

Endocrino Diabet & Metabol

View full text Add to dashboard Cite

show abstract

“…This stepped‐care approach can substantially delay HbA1c goal attainment in patients who ultimately require two or more AHAs for optimal glycaemic control. A recent analysis of observational data in the United Kingdom indicated that only 25% of patients with T2D with HbA1c ≥53 mmol/mol (≥7.0%) received treatment intensification within 12 months . Further, the likelihood of attaining glycaemic control was significantly lower for patients with delayed intensification.…”

Section: Introductionmentioning

confidence: 99%

Double‐blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT‐M study

Frías

Zimmer

Lam

et al. 2019

Diabetes Obesity Metabolism

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Aims To characterize the glycaemic efficacy and safety of initiation of the dipeptidyl peptidase‐4 inhibitor sitagliptin during metformin dose escalation in people with type 2 diabetes (T2D) not at glycated haemoglobin (HbA1c) goal on a sub‐maximal dose of metformin. Materials and methods Study participants with HbA1c ≥58 mmol/mol and ≤97 mmol/mol (≥7.5% and ≤11.0%) while on 1000 mg/d metformin were randomized to sitagliptin 100 mg once daily or placebo. All were to uptitrate metformin to 2000 mg/d. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is superior to placebo when initiated during uptitration of metformin in reducing HbA1c at week 20. [ ClinicalTrials.gov Identifier: NCT02791490, EudraCT: 2015‐004224‐59] Results A total of 458 participants (mean HbA1c 71.1 mmol/mol [8.7%], T2D duration 6.3 years) were treated. After 20 weeks, the least squares (LS) mean changes from baseline in HbA1c were −12.1 mmol/mol (−14.0, −10.1) (−1.10% [−1.28, −0.93]) and −7.6 mmol/mol (−9.6, −5.6) (−0.69% [−0.88, −0.51]) with sitagliptin and placebo, respectively; the between‐group difference in LS mean changes from baseline HbA1c was −4.5 mmol/mol (−6.5, −2.5) (−0.41% [−0.59, −0.23]); P < 0.001. The likelihood of having HbA1c <53 mmol/mol (<7.0%) at week 20 was higher in the sitagliptin group than in the placebo group in the overall population (relative risk 1.7, P = 0.002) and in those with a baseline HbA1c ≥69 mmol/mol (≥8.5%) (relative risk 2.4, P = 0.026). There were no notable differences between groups with regard to adverse events overall, hypoglycaemia events, changes in body weight or other safety variables. Conclusion In participants not at HbA1c goal on a sub‐maximal dose of metformin, addition of sitagliptin at the time of metformin dose uptitration improved glycaemic response and HbA1c goal attainment, with similar safety and tolerability, compared to metformin uptitration alone.

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“…Delays in anti‐hyperglycaemic treatment intensification (TI) are common and often result in exposure to unnecessarily high levels of A1C that can last for months or even years . Following TI, these delays have been shown to be associated with poorer response to the additional therapy . Thus, delaying TI exposes patients to avoidable hyperglycaemia, both during and after the delays.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] Following TI, these delays have been shown to be associated with poorer response to the additional therapy. [5][6][7][8] Thus, delaying TI exposes patients to avoidable hyperglycaemia, both during and after the delays. There are many reasons why patients and their clinicians do not intensify therapy in a timely manner, including fear of insulin (needle anxiety), 9 competing demands at clinical encounters, 10 polypharmacy, 11 costs and costsharing issues, 12,13 health system barriers, 13 and clinical inertia.…”

Section: Introductionmentioning

confidence: 99%

Delays in anti‐hyperglycaemic therapy initiation and intensification are associated with cardiovascular events, hospitalizations for heart failure and all‐cause mortality

Nichols

Romo‐LeTourneau

Vupputuri

et al. 2019

Diabetes Obesity Metabolism

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Aims The aims of this study were to assess the impact of delays in treatment intensification (TI) on cardiovascular events, heart failure, and all‐cause mortality at typical stages of anti‐hyperglycaemic therapy. Materials and Methods Using electronic health record data, we created three TI cohorts of diabetes patients who: 1) initiated metformin (MET) as their first anti‐hyperglycaemic therapy; 2) added a sulfonylurea (SU) to MET; and 3) initiated insulin (INS) while using MET or SU, alone or in combination. Primary exposure variables were haemoglobin A1C value preceding cohort therapy (pre‐TI A1C) and time to intensification, that is, the time between pre‐TI A1C >7% and cohort index date. Cox regression models were used to analyse the associated risk of cardiovascular events, hospitalizations for heart failure and all‐cause mortality. Results In the MET cohort, each additional percentage point of pre‐TI A1C was associated with a 10% increased risk of a CV event (HR, 1.10; 95% CI, 1.03–1.07; P = 0.004), a 7% increased risk of HF hospitalization (HR, 1.07; 95% CI, 1.01–1.14; P = 0.034) and a 7% increased risk of all‐cause mortality (HR, 1.07; 95% CI, 1.01–1.14; P = 0.032). Pre‐TI A1C was associated with a 9% increased risk of a CV event in the INS cohort (HR,1.09; 95% CI, 1.04–1.13; P < 0.001). Each month of delay in TI was significantly associated with a 6% increased risk of hospitalization for HF (HR, 1.06; 95% CI, 1.00–1.13; P = 0.040) and all‐cause mortality (HR, 1.06; 95% CI, 1.00–1.13; P = 0.050) in the MET cohort. Conclusions Delays in TI were associated with poor outcomes over a mean follow‐up period of nearly five years. Earlier initiation and more rapid intensification of pharmacotherapy could reduce the risk of poor outcomes.

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Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes

Abstract: Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.

Cited by 41 publications

References 26 publications

Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis

Clinical implications of prolonged hyperglycaemia before basal insulin initiation in type 2 diabetes patients: An electronic medical record database analysis

Double‐blind, randomized clinical trial assessing the efficacy and safety of early initiation of sitagliptin during metformin uptitration in the treatment of patients with type 2 diabetes: The CompoSIT‐M study

Delays in anti‐hyperglycaemic therapy initiation and intensification are associated with cardiovascular events, hospitalizations for heart failure and all‐cause mortality

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