Stefan Pscherer

Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care.

Aim Type 2 diabetes is associated with an increased risk of fractures. There are a few studies on the effects of diabetes treatment on fracture risk. The aim was to investigate the fracture risk related to various types of insulin therapy in primary care practices. Methods Data from 105,960 type 2 diabetes patients from 1,072 general and internal medicine practices in Germany were retrospectively analyzed (Disease Analyzer database; 01/2000–12/2013). Fracture risk of the following therapies was compared using multivariate logistic regression models adjusting for age, sex, diabetes care, comorbidity, and glycemic control (HbAlc): 1) incident insulin therapy versus oral antidiabetic drugs, 2) basal-supported oral therapy versus supplementary insulin therapy versus conventional insulin therapy, and 3) insulin glargine versus insulin detemir versus NPH insulin. Results There was a lower odds of having incident fractures in the oral antidiabetic drug group compared to incident insulin users, although not significant (odds ratio [OR]; 95% confidence interval: 0.87; 0.72–1.06). There were increased odds for conventional insulin therapy (OR: 1.59; 95% CI [confidence interval] 0.89–2.84) and supplementary insulin therapy (OR: 1.20; 0.63–2.27) compared to basal-supported oral therapy, which was not significant as well. Overall, there was no significant difference in fracture risk for basal insulins (glargine, detemir, NPH insulin). After a treatment duration ≥2 years, insulin glargine showed a lower odds of having ≥1 fracture compared to NPH users (OR: 0.78; 0.65–0.95) (detemir vs NPH insulin: OR: 1.03; 0.79–1.36). Conclusion Long-standing therapy with insulin glargine was associated with a lower odds of having any fractures compared to NPH insulin. Further studies are required to investigate whether the lower chance is due to a reduced frequency of hypoglycemia.

Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis

AIMSnTo compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin.nnnMETHODSnIn the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008-2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan-Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance.nnnRESULTSnIn BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31-1.87; NPH vs. glargine: 1.22; 1.07-1.38). Heart failure (1.39; 1.16-1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98-0.99), metformin (0.61; 0.54-0.69), and sulfonylurea co-medication (0.86; 0.77-0.97) were associated with lower discontinuation.nnnCONCLUSIONSnIn BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.

Composite efficacy parameters and predictors of hypoglycaemia in basal-plus insulin therapy—a combined analysis of 713 type 2 diabetic patients

We aimed to identify predictors of hypoglycaemia in patients with poorly controlled type 2 diabetes treated with a single daily bolus of insulin glulisine on top of insulin glargine and oral antidiabetic drugs (basal‐plus regimen).

In Type 2 Diabetes Patients, Insulin Glargine is Associated with Lower Postprandial Release of Intact Proinsulin Compared with Sulfonylurea Treatment:

Objective: Our objective was to investigate how postprandial processing of intact proinsulin is influenced by different pharmacological strategies in type 2 diabetes mellitus (T2DM). Materials/Methods: This exploratory, nonrandomized, cross-sectional study recruited T2DM patients and healthy subjects. Upon recruitment, eligible T2DM patients had been treated for ≥6 months with insulin glargine (GLA) plus metformin (MET), sulfonylureas (SU) plus MET, or dipeptidyl-peptidase-4 inhibitors (DPP-4-I) plus MET. Blood samples were drawn from study participants after an 8 h fast and at regular intervals for up to 5 h after consumption of a standardized meal. Study endpoints included postprandial intact proinsulin and insulin levels and the insulin/proinsulin ratio. Results: As expected, postprandial secretion of proinsulin was greater in all T2DM treatment groups than in healthy subjects (p < .01 for all comparisons). Postprandial release of proinsulin was significantly greater in T2DM patients treated with SU plus MET than in those treated with GLA plus MET (p = .003). Treatment with DPP-4-I plus MET was associated with reduced proinsulin secretion versus SU plus MET and an increased insulin/proinsulin ratio versus the other T2DM groups. Conclusions: Treatment of T2DM with GLA plus MET or DPP-4-I plus MET was associated with a more physiological postprandial secretion pattern of the β cell compared with those treated with SU plus MET.

Diabetes treatment in people with type 2 diabetes and schizophrenia: Retrospective primary care database analyses

AIMSnAim of this study were to compare outcomes (HbA1c, BMI) and antidiabetic treatment of type 2 diabetes patients with and without schizophrenia under real-life conditions in primary care practices in Germany.nnnMETHODSn1321 type 2 diabetes patients with and 1321 matched controls (age, sex, diabetes duration, diabetologist care, practice) without schizophrenia in 1072 general practices throughout Germany were retrospectively analyzed (Disease Analyser: 01/2009-12/2013). Antidiabetic treatment, HbA1c and BMI were compared using paired t-tests, McNemar tests and conditional logistic regression adjusting for macro- and microvascular comorbidity (ICD-10).nnnRESULTSnMean age (±SD) of patients and controls was 67.4±13.2 years (males: 38.9%). Diabetes duration was 5.7±4.3 years, 6% were in diabetologist care. Private health insurance was less often found among patients with schizophrenia than controls (2.2% vs 6.3%; p<0.0001). There was no difference in the mean HbA1c values (cases: 7.1±1.4%; controls: 7.2±1.5%) (54.1 vs. 55.2 mmol/mol) (p=0.8797) and in the average BMI (32.4±6.6 vs. 31.0±5.0 kg/m(2); p=0.2072) between the two groups. Novel cost-intensive antidiabetic agents (DPP-4- or SGLT2-inhibitors, GLP-1 receptor agonists) were less often prescribed in cases (15.3 vs. 18.3%; p=0.0423). However, in multivariable logistic regression, schizophrenia (odds ratio, 95%CI: 1.101; 0.923-1.317) was not associated with prescription use of novel antidiabetic agents (reference: other antidiabetic agents) after adjusting for private health insurance (OR: 2.139; 1.441-3.177) and comorbidity.nnnCONCLUSIONSnThere is no evidence that type 2 diabetes patients with schizophrenia have worse diabetes control than those without a severe mental illness in general practices.

Changes in Glycemic Control and Body Weight After Initiation of Dapagliflozin or Basal Insulin Supported Oral Therapy in Type 2 Diabetes: A Primary Care Database Study

Background: The aim was to compare changes in HbA1c and body weight after initiation of dapagliflozin or basal insulin supported oral therapy (BOT) in type 2 diabetes patients in primary care practices. Methods: Patients from 983 primary care practices who started dapagliflozin or BOT between December 2012 and July 2015 (index date, ID) were retrospectively analyzed (Disease Analyzer; Germany). Changes in HbA1c (%) and body weight (kg) were evaluated 90-270 days after ID. Propensity score (PS) matching (1:1) was used to adjust for differences in baseline clinical characteristics (180-0 days before ID: age, sex, health insurance, diabetologist care, glucose lowering therapy, HbA1c, body mass index) and duration (days) between start of therapies and last HbA1c or weight documentation after ID. Results: After PS matching, 766 dapagliflozin (mean ± SD; age: 63 ± 10 years; HbA1c: 8.9 ± 1.2%) and 766 BOT (age: 63 ± 10 years; HbA1c: 8.7 ± 1.1%) patients were included. HbA1c decreased by mean (SD) of 1.0% (1.3) in dapagliflozin and by 1.0% (1.4) in BOT patients after 90-270 days (HbA1c reduction; dapagliflozin vs BOT: –0.01%; P = .79). In 440 dapagliflozin users with available data, body weight (97.4 ± 19.9 kg) decreased by 3.1 (5.8) kg after 90-270 days, whereas no significant weight change was observed in 440 matched BOT patients (97.5 ± 19.9 kg) (weight reduction; dapagliflozin vs BOT: –3.0 kg; P < .05). Conclusions: Initiation of dapagliflozin therapy reduced HbA1c similar to basal insulin with the additional benefit of weight reduction in type 2 diabetes patients treated in general practices.

Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment - A prospective observational study in 2202 patients.

AIMnOptimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA).nnnMETHODSnThis was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus).nnnRESULTSnA total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups.nnnCONCLUSIONnThese findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic target on BOT with insulin glargine is equally safe and effective using either long-acting insulin titration alone or the addition of a rapid-acting insulin analogue.

Effectiveness and tolerability of treatment intensification to basal-bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study.

Background Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice. Methods This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT). Results A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1). Conclusion Intensifying glargine-based BOT or glulisine-based SIT to a BBT regimen in poorly controlled T2DM patients in daily routine care led to marked improvements of glycemic control and was well tolerated.

Titration and optimization trial for the initiation of insulin glargine 100 U/mL in inadequately controlled type-2 diabetes patients on oral antidiabetic drugs

For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal insulin is recommended, but titration and optimization of basal insulin therapy in primary care is not well understood. We conducted an observational trial in 2470 patients with T2DM who initiated insulin glargine 100 U/L (Gla‐100) on top of oral antidiabetic drugs. Physicians were free to choose either a “Davies,” “Fritsche” or “individual” titration algorithm. We found that fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels were effectively reduced by Gla‐100; 65.9% of patients achieved the primary endpoint (FBG ≤6.1 mmol/L (110 mg/dL) or an individual HbA1c target). There were no significant differences in efficacy and safety between the algorithms used. The mean FBG decreased by 3.2 mmol/L (59 mg/dL) over 12 months, while the mean HbA1c decreased by 15.3 mmol/mol (1.4%)%. From a starting dose of 11.7 U/d, the Gla‐100 dosage was 22.8 U/d at 12 months, with similar values in each group. Rates of hypoglycaemia were low and did not differ by titration algorithm. We conclude that Gla‐100 was effective at reducing FBG and HbA1c, independent of the titration algorithm, but observed that algorithms were inconsistently applied in clinical practice.