Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review

Khunti, Kamlesh; Gomes, Marı́lia B.; Pocock, Stuart J.; Shestakova, Marina V.; Pintat, Stéphane; Fenici, Peter; Hammar, Niklas; Medina, Jesús

doi:10.1111/dom.13088

Cited by 297 publications

(306 citation statements)

References 77 publications

(346 reference statements)

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“…As with lower‐middle and upper‐middle‐income countries, this finding may reflect delays in treatment intensification but for different reasons. A possible contributing factor is conservative management of patients by clinicians, as has been documented previously . In addition, the current stepwise approach to treatment intensification that is advocated by major treatment guidelines may lead to prolonged periods of hyperglycaemia in between steps .…”

Section: Discussionmentioning

confidence: 98%

“…Treatment intensification is recommended when patients remain above their HbA1c targets for >3 months after the last intervention. Despite these recommendations, available data, mainly from Europe and North America, indicate poor attainment of glycaemic targets and infrequent implementation of timely treatment intensification . Moreover, real‐world data on the management of T2D are scarce in many low‐ and middle‐income countries, in which the rising disease prevalence is a concern.…”

Section: Introductionmentioning

confidence: 99%

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Glycaemic control in patients with type 2 diabetes initiating second‐line therapy: Results from the global DISCOVER study programme

Khunti

Chen

Cid‐Ruzafa³

et al. 2019

Diabetes Obesity Metabolism

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Aim To assess glycaemic control and factors associated with poor glycaemic control at initiation of second‐line therapy in the DISCOVER programme. Materials and methods DISCOVER (NCT02322762 and NCT02226822) comprises two similar prospective observational studies of 15 992 people with type 2 diabetes (T2D) initiating second‐line glucose‐lowering therapy in 38 countries across six regions (Africa, Americas, South‐East Asia, Eastern Mediterranean, Europe and Western Pacific). Data were collected using a standardized case report form. Glycated haemoglobin (HbA1c) levels were measured according to standard clinical practice in each country, and factors associated with poor glycaemic control (HbA1c >8.0%) were evaluated using hierarchical regression models. Results HbA1c levels were available for 80.9% of patients (across‐region range [ARR] 57.5%‐97.5%); 92.2% (ARR 59.2%‐99.1%) of patients had either HbA1c or fasting plasma glucose levels available. The mean HbA1c was 8.3% (ARR 7.9%‐8.7%). In total, 26.7% of patients had an HbA1c level ≥9.0%, with the highest proportions in South‐East Asia (35.6%). Factors associated with having HbA1c >8.0% at initiation of second‐line therapy included low education level, low country income, and longer time since T2D diagnosis. Conclusions The poor levels of glycaemic control at initiation of second‐line therapy suggest that intensification of glucose‐lowering treatment is delayed in many patients with T2D. In some countries, HbA1c levels are not routinely measured. These findings highlight an urgent need for interventions to improve monitoring and management of glycaemic control worldwide, particularly in lower‐middle‐ and upper‐middle‐income countries.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Glycaemic control in patients with type 2 diabetes initiating second‐line therapy: Results from the global DISCOVER study programme

Khunti

Chen

Cid‐Ruzafa³

et al. 2019

Diabetes Obesity Metabolism

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“…Significant covariates were HbA1c concentrations at baseline, duration with diabetes and attainment of higher education. The increase in antidiabetic medication prescribed to the SMBG cohort over the course of the present study illustrates the potential of obtaining and using BG profiles to facilitate a more targeted approach to prescribing and to overcome the issue of clinical inertia in the treatment of hyperglycaemia in Type 2 diabetes [31]. HR, hazard ratio; SMBG, self-monitoring of blood glucose.…”

Section: Discussionmentioning

confidence: 76%

Effect of structured self‐monitoring of blood glucose, with and without additional TeleCare support, on overall glycaemic control in non‐insulin treated Type 2 diabetes: the SMBG Study, a 12‐month randomized controlled trial

et al. 2019

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Aim To examine the impact of structured self‐monitoring of blood glucose, with or without TeleCare support, on glycaemic control in people with sub‐optimally controlled Type 2 diabetes. Methods We conducted a 12‐month, multicentre, randomized controlled trial in people with established (>1 year) Type 2 diabetes not on insulin therapy, with sub‐optimal glycaemic control [HbA1c ≥58 to ≤119 mmol/mol (≥7.5% to ≤13%)]. A total of 446 participants were randomized to a control group (n =151) receiving usual diabetes care, a group using structured self‐monitoring of blood glucose alone (n =147) or a group using structured self‐monitoring of blood glucose with additional monthly ‘TeleCare’ support (n =148). The primary outcome was HbA1c at 12 months. Results A total of 323 participants (72%) completed the study; 116 (77%) in the control group, 99 (67%) in the self‐monitoring of blood glucose alone group and 108 (73%) in the self‐monitoring of blood glucose plus TeleCare group. Compared to baseline, the mean HbA1c was lower in all groups at 12 months, with reductions of 3.3 mmol/mol (95% CI –5.71 to –0.78) or 0.3% (95% CI –0.52 to –0.07; P=0.01) in the control group, 11.4 mmol/mol (95% CI –14.11 to –8.76) or 1.1% (–1.29 to –0.81; P<0.0001) in the group using self‐monitoring of blood glucose alone and 12.8 mmol/mol (95% CI –15.34 to –10.31) or 1.2% (95% CI –1.40 to ‐0.94; P<0.0001) in the group using self‐monitoring of blood glucose plus TeleCare. This represents a reduction in HbA1c of 8.9 mmol/mol (95% CI –11.97 to –5.84) or 0.8% (95% CI –1.10 to ‐0.54; P≤0.0001) with structured self‐monitoring of blood glucose compared to the control group. Participants with lower baseline HbA1c, shorter duration of diabetes and higher educational achievement were more likely to achieve HbA1c ≤53 mmol/mol (7.0%). Conclusions Structured self‐monitoring of blood glucose provides clinical and statistical improvements in glycaemic control in Type 2 diabetes. No additional benefit, over and above the use of structured self‐monitoring of blood glucose, was observed in glycaemic control with the addition of once‐monthly TeleCare support. (Clinical trial registration no.: ISRCTN21390608)

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“…This is a common, long‐recognized factor limiting HbA1c goal attainment in many patients with T2D, attributed to multiple clinician‐related factors including lack of treatment target awareness and concerns regarding patient adherence and potential for medication side effects . Multiple studies, including those in patients on metformin monotherapy, have demonstrated median delays in excess of 1 year to appropriate treatment intensification for patients with T2D not at HbA1c goal . Given its multifactorial nature, clinical inertia is a challenging issue to address; however, safe, effective and convenient treatment‐intensification strategies should be enabling in this regard.…”

Section: Discussionmentioning

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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Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review

Cited by 297 publications

References 77 publications

Glycaemic control in patients with type 2 diabetes initiating second‐line therapy: Results from the global DISCOVER study programme

Glycaemic control in patients with type 2 diabetes initiating second‐line therapy: Results from the global DISCOVER study programme

Effect of structured self‐monitoring of blood glucose, with and without additional TeleCare support, on overall glycaemic control in non‐insulin treated Type 2 diabetes: the SMBG Study, a 12‐month randomized controlled trial

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

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