Long-term sustainability of glycaemic achievements with second-line antidiabetic therapies in patients with type 2 diabetes: A real-world study.

To inform patients and their carers about both the probability of reducing glycated haemoglobin (HbA1c) to clinically desirable levels and the sustainability of such control over 2 years with major second-line antidiabetic therapies, in individual risk scenarios, with and without third-line intensification. From US Centricity Electronic Medical Records, 163 081 patients with type 2 diabetes aged 18 to 80 years, who had initiated metformin, intensified their treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), sulphonylureas (SUs), insulin or thiazolidinediones (TZDs), and continued second-line treatment for ≥6 months, were selected. Treatment groups were balanced with regard to baseline characteristics, and glycaemic achievements were estimated using logistic regression analysis. With HbA1c concentrations of 58-63.9 mmol/mol (7.5-7.9%) at second-line treatment initiation, the adjusted probabilities of achieving HbA1c <53 mmol/mol (<7%) at 6 months were 32%, 38%, 39%, 26% and 38% in the SU, DPP-4 inhibitor, GLP-1RA, insulin and TZD groups, respectively, while with baseline HbA1c concentrations of 64-75 mmol/mol (8-9%), the corresponding probabilities of reducing HbA1c to <58 mmol/mol (<7.5%) were 38%, 44%, 40%, 34% and 42%, respectively. In these baseline HbA1c categories, the adjusted probabilities of sustaining HbA1c achievements over 2 years were higher in the GLP-1RA and TZD groups, compared with the SU and insulin groups (P < .01). With baseline HbA1c concentrations of 75.1-108 mmol/mol (9.1-12%) 38% of patients achieved an HbA1c concentration <58 mmol/mol (<7.5%) at 6 months. The adjusted probability of sustaining this control over 2 years was higher in the incretin and TZD groups (range 62%-75%), while insulin and SUs offered lower chances of sustainable control (range 54%-56%). Patients treated with second-line incretins and TZDs had a significantly higher probability of achieving and sustaining glycaemic control over 2 years without further intensification, compared with those treated with SUs or insulin.

Montvida O ，Shaw JE ，Blonde L ，Paul SK ... -  《-》

Change in glycated haemoglobin levels after initiating second-line therapy in type 2 diabetes: a primary care database study.

The aim of the present study was to compare the absolute reduction in glycated haemoglobin (HbA1c) levels at 6 months after initiating second-line glucose-lowering therapy in patients with type 2 diabetes treated with metformin monotherapy in general practices. A total of 7009 patients were identified (Disease Analyser Germany: January 2004 to December 2014). The patients' mean ± standard deviation (s.d.) age was 63 ± 11 years, 55.5% were male and their mean ± s.d. HbA1c level was 8.0 ± 1.6%. The initiated second-line therapies included: dipeptidyl peptidase-4 (DPP-4) inhibitors (38.7%); sulphonylureas (36.3%); insulin (13.3%); glucagon-like peptide-1 receptor agonists (GLP-1RAs; 2.5%); thiazolidinediones (5%); and other agents (glinides, aldose-reductase inhibitors; 4.1%). The mean absolute HbA1c change from baseline was -0.9% (DPP-4 inhibitors, -0.9%; sulphonylureas, -0.9%; insulin, -1.1%; GLP-1RAs, -0.7%; thiazolidinediones, -0.9%; and other, -0.7%; all p < 0.001). Overall, 58% of patients reached the HbA1c target of <7% (DPP-4 inhibitors, 61.7%; sulphonylureas, 56.7%; insulin, 45.6%; GLP-1RAs, 62.2%; thiazolidinediones, 69.7%; and other, 57.5%). Compared with sulphonlyureas, DPP-4 inhibitors, GLP-1RAs and thiazolidinediones were associated with an increased odds of reaching HbA1c <7% [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.09-1.40; OR 1.43, 95% CI 1.01-2.04; and OR 1.70, 95% CI 1.30-2.23, respectively], whereas insulin was related to a lower odds (0.66, 95% CI 0.55-0.78). In conclusion, in patients with type 2 diabetes very similar reductions in HbA1c after 6 months of second-line therapy were achieved regardless of the type of therapy.

Rathmann W ，Bongaerts B ，Kostev K 《-》

Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

To identify the time to and patient characteristics associated with treatment intensification in patients with type 2 diabetes (T2D) and poor glycaemic control. Using a large US insurance claims database, we conducted a retrospective cohort study among adult patients with T2D and glycated haemoglobin (HbA1c) ≥8% (index date) after ≥3 months of therapy including metformin. Patients were required to have continuous enrolment for at least 12 months before (baseline) and after index date, and no injectable antidiabetes medications. We defined treatment intensification as prescription fill for injectable or additional oral antidiabetic drugs (OADs). Cox modelling was performed to identify factors associated with time to treatment intensification. For the 11 525 patients meeting the inclusion criteria, the mean age at index date was 57 years, 40% were female and the mean index HbA1c was 9.1%. Overall, 37% of patients had their treatment intensified <6 months after, 11% had their treatment intensified 6-12 months after, and 52% did not have their treatment intensified <12 months after the index date. A higher index HbA1c was associated with early intensification [hazard ratio (HR) 1.18 for HbA1c ≥9 to <10% and HR 1.41 for HbA1c ≥10% compared with HbA1c ≥8 to <9%; p < 0.0001), and later line of therapy was associated with late intensification (HR 0.78 for metformin with one OAD and HR 0.68 for metformin with ≥2 OADs compared with metformin monotherapy; p < 0.0001). Fewer than half of patients with T2D and treatment failure received intensification within 12 months in a real-world US population. Factors associated with treatment inertia can be used to target clinical care for these patients.

Fu AZ ，Sheehan JJ 《-》

Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes.

Thomsen RW ，Baggesen LM ，Søgaard M ，Pedersen L ，Nørrelund H ，Buhl ES ，Haase CL ，Johnsen SP ... -  《-》

Sodium-glucose co-transporter-2 inhibitors, the latest residents on the block: Impact on glycaemic control at a general practice level in England.

To determine, using published general practice-level data, how differences in Type 2 diabetes mellitus (T2DM) prescribing patterns relate to glycaemic target achievement levels. Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of different classes of medication in 2015/2016 and changes between that year and the year 2014/2015 in medication to proportion of patients achieving target glycaemic control (glycated haemoglobin A1c [HbA1c] ≤58 mmol/mol [7.5%]) and proportion of patients at high glycaemic risk (HbA1c >86 mmol/mol [10.0%]) for practices in the National Diabetes Audit with >100 people with T2DM on their register. Overall, HbA1c outcomes were not different between the years studied. Although, in percentage terms, most practices increased their use of sodium-glucose co-transporter-2 (SGLT2) inhibitors (96%), dipeptidyl peptidase-4 (DPP-4) inhibitors (76%) and glucagon-like peptide 1 (GLP-1) analogues (53%), there was wide variation in the use of older and newer therapies. For example, 12% of practices used >200% of the national average for some newer agents. In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c ≤58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. In year-on-year analysis there was ongoing deterioration in glycaemic control, which was offset to some extent by increased use of SGLT2 inhibitors and GLP-1 analogues, which were associated with a greater proportion of patients achieving HbA1c levels ≤58 mmol/mol and a smaller proportion of patients with HbA1c levels >86 mmol/mol. SGLT2 inhibitor prescribing was associated with significantly greater improvements than those found for GLP-1 analogues. Greater use of newer agents was associated with improvement in glycaemic outcomes but was not sufficient to compensate for the prevailing decline. This may reflect wide variability in the prescribing of newer agents. We found that SGLT inhibitors may be superior to other oral agents in relation to HbA1c outcome. Serious consideration should be given to their use.

Heald AH ，Fryer AA ，Anderson SG ，Livingston M ，Lunt M ，Davies M ，Moreno GYC ，Gadsby R ，Young RJ ，Stedman M ... -  《-》