Therapeutic inertia in patients treated with two or more antidiabetics in primary care: <scp>F</scp>actors predicting intensification of treatment

Mata-Cases, Manel; Franch-Nadal, Josep; Real, Jordi; Gratacòs, Mónica; López‐Simarro, Flora; Khunti, Kamlesh; Mauricio, Dı́dac

doi:10.1111/dom.13045

Cited by 76 publications

(91 citation statements)

References 53 publications

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“…A multinational observational study including 17,374 participants documented pre‐insulin HbA1c values of 8.9 ± 1.6% . The reasons for delayed insulin initiation are multifactorial, including patient‐centred and physician‐related factors . Although TECOS participants appear to have fared slightly better, with lower HbA1c values at insulin initiation, this may reflect the selection of better controlled patients for the trial, more attentive care for trial participants than is seen in general practice, or contemporaneous guidelines recommending less stringent HbA1c targets for patients with diabetes and established cardiovascular complications .…”

Section: Discussionmentioning

confidence: 99%

Progression of glucose‐lowering diabetes therapy in TECOS

Bethel

Engel

Stevens

et al. 2018

Endocrino Diabet & Metabol

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Summary Aims TECOS was a randomized, double‐blind, placebo‐controlled trial assessing the impact of sitagliptin vs. placebo on cardiovascular outcomes when added to usual care in patients with type 2 diabetes. We report the use of concomitant diabetes medications and the risk for progression to insulin during follow‐up. Materials and Methods TECOS enrolled 14 671 participants with HbA1c 6.5%‐8.0% on monotherapy with metformin, pioglitazone, sulfonylurea (SU), or dual therapy with two oral agents or insulin with or without metformin. Subsequent diabetes management was by the participant's usual care physician. Time to initiation of insulin and risk of hypoglycaemia were estimated using Cox proportional hazards models. Results The most common glucose‐lowering regimens at baseline were metformin monotherapy (30.2%), SU monotherapy (8.5%), metformin/SU therapy (35.1%), and insulin with or without metformin (13.9% and 8.6%, respectively). Over a median 3.0 years’ follow‐up, diabetes therapy was intensified in 25.2% of participants (sitagliptin 22.0%, placebo 28.3%). Medications most commonly added were SU (8.3%) or insulin (8.8%). Insulin initiation in the usual care setting occurred at mean (standard deviation) HbA1c of 8.5 (1.5)%. Sitagliptin did not impact rates of severe hypoglycaemia, but delayed progression to insulin when added to metformin or metformin/SU regimens. Conclusion Consistent with the trial's pragmatic design, TECOS participants underwent typical progression of diabetes medications. Sitagliptin was associated with lower HbA1c, without increased risk for severe hypoglycaemia and was associated with delayed progression to insulin when added to metformin with or without SU.

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Section: Discussionmentioning

confidence: 99%

Progression of glucose‐lowering diabetes therapy in TECOS

Bethel

Engel

Stevens

et al. 2018

Endocrino Diabet & Metabol

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“…10 Briefly, data were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) electronic database, 11,12 covering the period between January 2010 and December 2014. 10 Briefly, data were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) electronic database, 11,12 covering the period between January 2010 and December 2014.…”

Section: Study Design and Data Sourcementioning

confidence: 99%

“…The main health provider in the region is the Catalan Health Institute (ICS), which operates around 280 primary healthcare centres (PCCs) with >3500 general practitioners (GP) who provide medical cover to 5.8 million subjects (which represent 80% of the region's population; 10% of Spain's population). 10,16 Intensification was defined as the prescription of a new antidiabetic drug during follow-up. These data, together with the dispensed treatments extracted from pharmacy-invoicing data provided by the Catalan Health Service (CatSalut), are further incorporated into an anonymized electronic general practice database available for researchers, the SIDIAP database, which started in 2005.…”

Section: Study Design and Data Sourcementioning

confidence: 99%

“…10,17 Poor glycaemic control was defined as an HbA1c value ≥7% as recommended by international and local guidelines, 3,5,16 and also ≥8% according to the pay-per-performance indicator of our institution (Catalan Institute of Health; ICS) in force during that period. We calculated the baseline CCI score in its abbreviated version using the eight categories of comorbidity (as recorded in the eCAP software) to create a score that reflects a cumulative increased likelihood of 1-year mortality.…”

Section: Study Variablesmentioning

confidence: 99%

“…4,5 While there are a significant number of randomized clinical trials (RCTs) and real-world studies showing the efficacy of different therapeutic agents in the second-line treatment for T2DM, data for the third-or fourth-line therapies remain scarce. 10 To our knowledge, few real-world studies have assessed the efficacy of the different agents used as the third or even fourth step of treatment, and even fewer have compared the use of insulin versus other antidiabetic drugs. 7 As a consequence, patients may persist with poor glycaemic control for long periods of time (months to years), 8 which is in turn associated with poor long-term outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Glycaemic control after treatment intensification in patients with type 2 diabetes uncontrolled on two or more non‐insulin antidiabetic drugs in a real‐world setting

Canivell

Mata-Cases

Real

et al. 2019

Diabetes Obesity Metabolism

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Aim: To assess glycaemic control after treatment intensification in patients with type 2 diabetes uncontrolled on ≥2 non-insulin antidiabetic drugs (NIADS).Methods: A retrospective cohort study, using electronic health records from the SIDIAP database (2010-2014), was conducted. Intensification was defined as the prescription of any new antidiabetic drug in patients treated with ≥2 NIADS and HbA1c >7%. The primary outcome was the absolute change in HbA1c 6-12 months after any intensification. Secondary analyses included the percentage of patients reaching HbA1c <7%, HbA1c <8%, and a reduction of HbA1c >1% after the first intensification.Results: There were 21 241 intensifications in 15 205 patients with a mean (SD) HbA1c of 9.02% (±1.35). Insulin and dipeptidyl peptidase-4 inhibitors (DPP4i) were the most frequently added therapies. The mean baseline-adjusted HbA1c reduction was 0.78% (95% CI, −0.80 to −0.76), varying from −0.69% with DPP4i to −0.85% with glucagon-like peptide-1 receptor agonists while the addition of insulin was associated with a reduction >1%.After the first intensification, 48.9% of patients achieved HbA1c <8%, 16.2% HbA1c <7%, and 43.1% a reduction >1%. High previous HbA1c was positively associated with the reduction of HbA1c >1% [odds ratio (OR) 2.13 (95% CI: 2.05-2.21)], but inversely associated with the attainment of HbA1c <7% [OR 0.64 (0.61-0.67)] or < 8% [OR 0.63 (0.60-0.65)]. Older age, male gender, higher Charlson index, and short diabetes duration were associated with achievement of HbA1c <7%.Conclusions: Despite intensification, most patients failed the glycaemic goal of HbA1c <7%. The reduction depended mainly on preintensification HbA1c values, with small differences between drugs. K E Y W O R D Sglycaemic control, intensification, observational, type 2 diabetes mellitus *Both authors contributed equally to this work.

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The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

Nair

Donnelly

Dawed

et al. 2020

Endocrino Diabet & Metabol

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Aim:To conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression. Methods:We conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.Results: Our search yielded 2785 articles; based on title, abstract and full-text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: 'Initiation of insulin', 'Initiation of oral antidiabetic drug', 'treatment intensification', 'antidiabetic therapy failure', 'glycaemic deterioration', 'decline in betacell function' and 'change in insulin dose'. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi-ethnic studies. Conclusion:We have identified the major determinants of diabetes progressionyounger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large-scale studies of diabetes progression in different ethnic groups. K E Y W O R D S diabetes progression, glycaemic deterioration, insulin initiation, type 2 diabetes S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Thakarakkattil Narayanan Nair A, Donnelly LA, Dawed AY, et al. The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus. Endocrinol Diab Metab. 2020;3:e00108.

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Therapeutic inertia in patients treated with two or more antidiabetics in primary care: Factors predicting intensification of treatment

Abstract: Intensification was not undertaken in 1 in 5 patients. Both HbA1c thresholds and time until therapy intensification exceeded current recommendations.

Cited by 76 publications

References 53 publications

Progression of glucose‐lowering diabetes therapy in TECOS

Progression of glucose‐lowering diabetes therapy in TECOS

Glycaemic control after treatment intensification in patients with type 2 diabetes uncontrolled on two or more non‐insulin antidiabetic drugs in a real‐world setting

The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

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