Preventive strategies in endocrinology focus on five major fields (the big five): thyroid gland disorders, obesity and diabetes mellitus, dyslipidemia, arterial hypertension and osteoporosis. These highly prevalent conditions have a high morbidity and mortality. As many can be prevented by relatively simple nonpharmacological measures or effectively mitigated by low-threshold pharmacological interventions, they represent model diseases for prevention in internal medicine. This article outlines the current options and discusses them in the context of current prevention strategies. Endocrine and diabetic diseases are among the most common and consequential chronic disorders in industrialized countries and essentially contribute to the total morbidity and mortality. Principal preventive strategies include structural prevention (environmental prevention), such as promoting anti-adipogenic and anti-diabetogenic social structures and behavioral prevention. The emphasis of preventive strategies is on population-related measures, structured screening programs and evidence-based lifestyle interventions. Based on current epidemiological data and guidelines, practical approaches are presented, ranging from iodine prophylaxis, lipid and blood pressure screening to promotion of healthy bone and obesity preventive structures. The concepts discussed demonstrate that effective endocrine and diabetological prevention requires coordinated action across clinical medicine, public health and health policy to realize its full potential.

AIMS:This real-world study evaluated the effectiveness and safety of switching basal insulin (BI) to insulin glargine 300 U/mL (Gla-300) in adults with inadequately controlled type 2 diabetes mellitus (T2DM), previously receiving basal-supported oral therapy plus prandial insulin (BOTplus) or multiple (≥3) daily injections (MDI) of short-acting insulins. MATERIALS AND METHODS:This non-interventional, multicentre, open-label, prospective 12-month study in Germany included adult participants (≥18 years) with T2DM, HbA1c between 7.5% and 10.0%, and fasting plasma glucose (FPG) >130 mg/dL (>7.2 mmol/L). The participants were switched from non-Gla-300 BOTplus or MDI regimen (including Gla-100, IDet, IDeg, or NPH) to Gla-300. The primary endpoint was the duration of glycaemic target achievement, defined as the time between ≥2 FPG values ≤110 mg/dL (≤6.1 mmol/L) or ≥1HbA1c value below the predefined target. RESULTS:Of 1217 participants, 582 completed the documentation of the 12-month Gla-300 treatment (FAS2-M12). Target achievement with Gla-300 was reported for 280/582 FAS2-M12 participants (48.1%). The median response duration was 295 days (95% CI: 226, 381). The mean (±SD) change in HbA1c and FPG from baseline was -0.56% (±1.08; n = 568) and -29.3 mg/dL or 1.63 mmol/L (±54.95; n = 540) at month 12, respectively (p < 0.0001). Numbers and incidence of hypoglycaemia were similar before starting Gla-300 therapy and at month 12. Body weight (100.1 kg ± 21.07; n = 571 at baseline) remained unchanged until month 12 (mean change: -0.0 kg ± 8.40; n = 513). CONCLUSIONS:Switching BI to Gla-300 from a BOTplus or MDI regimen with prior insulin Gla-100, IDeg, IDet, or NPH improved glycaemic control in participants with inadequately controlled T2DM over 12 months without increasing hypoglycaemia risk or weight gain.

Die Präventionsfelder in der Endokrinologie umfassen fünf wichtige Bereiche („The Big Five“): Schilddrüsenerkrankungen, Adipositas und Diabetes mellitus, Fettstoffwechselstörungen, arterielle Hypertonie und Osteoporose. Diese Krankheitsbilder sind häufige „Volkskrankheiten“ und weisen eine hohe Folgemorbidität und -mortalität auf. Sie lassen sich zum Teil durch relativ einfache nichtpharmakologische Maßnahmen vermeiden oder durch niederschwellige pharmakologische Interventionen in ihren Auswirkungen deutlich verringern, sodass sie generell Modellkrankheiten für die Prävention und Vorsorge darstellen. Diesbezügliche Optionen werden in unserem Beitrag aufgezeigt und im Kontext der derzeitigen Präventionsstrategien diskutiert. Endokrine und diabetologische Erkrankungen zählen zu den häufigsten und folgenschwersten chronischen Erkrankungen in industrialisierten Ländern und tragen maßgeblich zur Gesamtmorbidität und -mortalität bei. Prinzipielle Präventionsstrategien umfassen die Verhältnisprävention, beispielsweise die Förderung „antiadipogener“ und „antidiabetogener“ Gesellschaftsstrukturen, sowie die Verhaltensprävention. Im Vordergrund der Präventionsstrategien stehen populationsbezogene Maßnahmen, strukturierte Screeningprogramme und evidenzbasierte Lebensstilinterventionen. Anhand aktueller epidemiologischer Daten und Leitlinien werden konkrete Maßnahmen und Erfahrungen beschrieben – von der Jodprophylaxe über Lipid- und Blutdruckscreening bis hin zu knochengesundheitsfördernden und adipositaspräventiven Maßnahmen. Die dargestellten Konzepte zeigen, dass endokrinologische und diabetologische Prävention nur im Zusammenspiel von Medizin, Public Health und Gesundheitspolitik ihr volles Potenzial entfalten kann.

AIMS:This study assessed efficacy and safety of the fixed ratio combination iGlarLixi 100/33 (insulin glargine 100 U/mL plus lixisenatide 33 μg/mL) in people with type 2 diabetes (PwT2D) in daily clinical practice. MATERIALS AND METHODS:This non-interventional, multicentre, prospective, single-arm 24-week study documented PwT2D with an HbA1c of 7.5%-10.0%, currently treated with a basal insulin supported oral therapy (BOT) in German primary care facilities, after the physician had decided to change treatment to iGlarLixi 100/33, independent of study participation. Primary end-point was the absolute change in HbA1c (%) from baseline. RESULTS:Of 93 participants included, 70 comprised the full analysis set for efficacy assessment. Approximately 24 weeks after switching to iGlarLixi 100/33 HbA1c (mean ± standard deviation) changed from 8.52 ± 0.82% by -0.74 ± 0.81% to 7.74 ± 0.76%, FPG from 174.3 ± 44.6 mg/dL (9.67 ± 2.48 mmol/L) by -32.9 ± 46.3 mg/dL (-1.83 ± 2.57 mmol/L) to 141.4 ± 34.1 mg/dL (7.85 ± 1.89 mmol/L) and body weight from 104.3 ± 22.5 kg by -3.0 ± 7.5 kg to 101.3 ± 21.6 kg (all p < 0.01). Furthermore, use of DPP4 inhibitors was significantly reduced from 34.8% to 6.8% of participants. Derived (from 7-point self-measured plasma glucose) time in range (TIR) increased and time above range (TAR) decreased after 24 weeks to target ranges (all p < 0.05). Flash glucose monitoring data of 20 patients showed similar patterns for TIR and TAR, respectively, and a reduction in time below range (p = 0.007). Hypoglycaemia events did not change significantly and were low in number. No severe hypoglycaemia was reported. CONCLUSIONS:Modifying antiglycaemic treatment from a BOT regimen to iGlarLixi 100/33 in suboptimal controlled PwT2D in daily clinical practice improved glycaemic control without increasing hypoglycaemia and with favourable body weight change.

Fragestellung: iGlarLixi, eine Fixkombination aus Insulin glargin 100 Einheiten/ml und Lixisenatid, bietet eine einmal täglich zu verabreichende Therapieoption zur Behandlungsintensivierung von unter BOT unzureichend eingestellten Typ-2-Diabetespatienten.

iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, is a once-daily treatment advancement option for Pw2D not at target on BOT. CHANCE investigated effectiveness and safety of switching the BI to iGlarLixi in daily clinical practice. Primary objective was to assess absolute change in HbA1c 24 weeks (W24) after switching to iGlarLixi. Secondary objectives included changes in fasting plasma glucose (FPG), bodyweight (BW), use of oral antidiabetic drugs (OADs), dose of previous BI, and hypoglycemia incidence. Overall, data from 70 Pw2D were analyzed. Mean BI dose was 38.9 units per day and individual target HbA1c was 6.9%. iGlarLixi was started with 30 dose steps per day (DS/d); at W24, mean dose was 41.6 DS/d. HbA1c decreased by -0.7% (P < 0.001), while FPG trended down by ~20 mg/dL. This was accompanied by a -3.0 kg decrease in BW (P = 0.442). Numbers of OADs used decreased markedly 24 weeks after switching to iGlarLixi (P < 0.05). Hypoglycemia incidence was low before and did not change significantly after switching to iGlarLixi. In conclusion, advancing BOT by switching the BI to iGlarLixi, improved glycemic control of Pw2D in daily clinical practice without BW gain and with low hypoglycemia incidence; however, titration was not sufficient to reach glycemic targets after 24 weeks. Disclosure T.Wiesner: Advisory Panel; Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Sanofi-Aventis Deutschland GmbH, Lilly Diabetes, Boehringer Ingelheim Inc., Abbott Diabetes, Novo Nordisk, Dexcom, Inc., Novartis. M.Pfohl: Advisory Panel; Boehringer Ingelheim and Eli Lilly Alliance, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Sanofi-Aventis Deutschland GmbH. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Sanofi-Aventis Deutschland GmbH. J.Müller: Employee; Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Bayer Inc., Inmunebio Inc. J.Seufert: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim Pharma GmbH&Co.KG, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Abbott Diabetes, Bayer Inc., Boehringer Ingelheim Pharma GmbH&Co.KG, Merck Sharp & Dohme Corp., Sanofi-Aventis Deutschland GmbH, Novartis, Novo Nordisk. Funding Sanofi-Aventis Deutschland GmbH

This study evaluated the effectiveness and safety of switching the basal insulin (BI) in a BI‐supported oral therapy (BOT) to insulin glargine 300 U/ml (Gla‐300) in adults with inadequately controlled type 2 diabetes (T2D).

Fragestellung In der DELIVER-High-Risk-Studie wurden bei Typ-2-Diabetespatienten mit hohem Hypoglykämierisiko unter Basalinsulinanaloga der ersten Generation die Langzeitergebnisse nach einem Wechsel zum Basalinsulinanalogon der zweiten Generation Gla-300 oder zu einem anderen Basalinsulinanalogon der ersten Generation (sonstige Wechsler) verglichen.

Fragestellung Vergleich von Insulin glargin 300 E / ml (Gla-300) und Insulin degludec 100 E / ml (IDeg-100) in Hinblick auf Wirksamkeit und Sicherheit, definiert als Prozentsatz der Zeit im Glukosezielbereich (70–180 mg / dl), gemessen mittels kontinuierlicher Glukoseüberwachung (CGM) bei Patienten mit T1 D in routinemäßiger klinischer Praxis in Spanien.

The IGLU-SIT study documented the effectiveness of initiating supplementary prandial insulin treatment (SIT) with insulin glulisine after failure of oral antidiabetic drugs alone in patients with type 2 diabetes (T2DM) in a real-world setting in Germany. The IGLU-SIT study was an open-label, prospective, multicentre, non-interventional study with an observation period of 12 ± 1 months. The primary objective was to determine the proportion of patients reaching their pre-defined glycosylated haemoglobin (HbA1c) goal at 3, 6, 9 and 12 months. Selected secondary objectives were absolute change in HbA1c, a 7-point blood glucose profile, and rate of hypoglycaemia. Data were evaluated overall and by age group (< 65, 65–74 and ≥ 75 years). Overall, 215 patients with T2DM were observed in 64 centres. Baseline HbA1c was 8.3%, and mean HbA1c target was 6.8% (baseline 8.1% and target 6.9% in patients ≥ 75 years). Individual HbA1c target attainment in patients peaked at 38.9% (95% confidence interval [CI] 32.1–46.1%) after 12 months; this was 45.9% in patients aged ≥ 75 years. The mean HbA1c reduction was 1.12 ± 1.05% (p < 0.0001) with only minor differences by age group. A 7-point blood glucose profile revealed significant reductions (p < 0.0001) at all time-points. The rate of confirmed symptomatic hypoglycaemia was 2.2% (95% CI 0.7–5.1) during the 12-month follow-up; rates were increased in patients aged ≥ 75 years (7.0%; 95% CI 1.5–19.1) as were the rates of adverse events (17.8 vs. 6.1%). Initiating SIT with insulin glulisine is an appropriate treatment option in patients whose T2DM is insufficiently controlled. Particular attention should be paid to elderly patients in whom higher attainment rates of treatment target were associated with adverse events. https://awbdb.bfarm.de ; Identifier: 6819; Date of registration: 23.06.2016

The IGLU-S study assessed the effectiveness of insulin glulisine after switching from human insulin/other rapid-acting insulin analogues in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in a real-world setting in Germany. Open-label, prospective, multicentre, non-interventional study in Germany. The primary outcome was proportion of patients reaching pre-defined glycosylated haemoglobin A1c (HbA1c) goal at 3, 6, 9 and 12 months. Secondary outcomes included absolute changes in HbA1c, rate of hypoglycaemia and 7-point blood glucose profiles. Overall, 432 (55 T1DM, 377 T2DM) patients were enrolled. Baseline HbA1c was 8.2% (T1DM) and 8.3% (T2DM); individual HbA1c targets were 6.8% and 6.9%, respectively. After insulin glulisine introduction, the proportion of patients achieving their individual HbA1c increased to 43.6% (T1DM) and 39.6% (T2DM) of patients at 12 months. At 12 months, mean HbA1c was reduced by 0.86 ± 1.03% (p < 0.0001) in T1DM and 1.01 ± 1.02 (p < 0.0001) in T2DM. The 7-point blood glucose profile showed a significant reduction in patients with T2DM (p< 0.0001) and a non-significant reduction in T1DM patients. Confirmed symptomatic hypoglycaemia was 5.7% (T1DM) and 1.6% (T2DM). There were no cases of severe hypoglycaemia. Switching prandial insulin to insulin glulisine resulted in improved effectiveness with 43.6% of T1DM and 39.6% of T2DM patients reaching their individual pre-defined HbA1c target within 1 year. Switching was safe and was associated with a low rate of hypoglycaemia and adverse events. https://awbdb.bfarm.de ; Identifier: 6818; Date of registration: 23.06.2016

AIM:To evaluate the effectiveness and safety of initiating basal insulin-supported oral therapy (BOT) with insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs (OADs). MATERIALS AND METHODS:This non-interventional, multi-centre, prospective 52-week study, conducted in Germany and Switzerland, documented patients with type 2 diabetes with an HbA1c of between 7.5% and 10.0%, currently treated with OADs, after the physician had decided to start a BOT regimen with Gla-300. The primary endpoint was the rate of achievement of the individualized predefined HbA1c target. RESULTS:Of 1748 patients included, 1153 comprised the full analysis set, of whom 721 completed documentation of 12 months of Gla-300 treatment. Twelve months after starting Gla-300, 49.9% achieved their individualized HbA1c target, and 61.1% achieved either their HbA1c target or a fasting plasma glucose (FPG) of ≤110 mg/dL. Mean HbA1c decreased by -1.22% ± 1.05% to 7.28% ± 0.92% and mean FPG by -51.5 (±48.63) mg/dl to 132.9 ± 33.0 mg/dL. Median duration of HbA1c target achievement was 341 days and probability to remain on target after 6 months was 81%. Hypoglycaemia incidence and rates remained low after 12 months of Gla-300 treatment; no severe or severe nocturnal hypoglycaemia was observed. Body weight remained unchanged. CONCLUSIONS:Starting a BOT regimen with Gla-300 allowed about 60% of 721 German and Swiss patients with inadequately controlled type 2 diabetes to achieve glycaemic control within 12 months in daily clinical practice. Glycaemic control was achieved without weight gain or increased risk of nocturnal or severe hypoglycaemia.

Aims Adequate insulin titration is crucial for optimal glycaemic control in type 2 diabetes (T2D). We aimed to explore the factors and outcomes associated with titration of glargine 100 U/mL (Gla-100) in patients uncontrolled on oral antidiabetic drugs (OAD) and initiating insulin therapy. Methods Patients from the Titration and Optimization (TOP)-1 registry were stratified by the magnitude of Gla-100 up-titration during the first month (no [< 1 Units (U)/day (d)], minimal [≥ 1 and < 5 U/d], moderate [≥ 5 and ≤ 8 U/d] and strong [> 8 U/d]). The primary endpoint was a fasting blood glucose (FBG) ≤ 110 mg/dL on ≥ 2 occasions and/or individual HbA1c target by 12 months. Results Of 2308 patients, 905, 715, 409 and 279 underwent no, minimal, moderate and strong titration, respectively. Age decreased across increasing titration groups ( p = 0.02) while body mass index (BMI) ( p < 0.0001), FBG ( p < 0.0001), and HbA1c ( p < 0.0001) increased. At 12 months, the proportions of patients achieving the primary endpoint were comparable across groups (66.1% overall), though a smaller proportion of no titration patients met both their individual HbA1c target and FBG ≤ 110 mg/dL compared to moderate and strong titration patients (20.1% vs. 27.2% and 26.2%, p = 0.033 and 0.023, respectively). HbA1c was also comparable, though FBG was higher in the no titration group (126.2 vs. 122.6, 121.5 and 120.9 mg/dL, p < 0.02). A similar, small reduction in body weight occurred in all groups; hypoglycaemia rates were comparable across groups. Conclusions In real-world, titration of Gla-100 during the first month appears to coincide with a number of baseline factors. Insulin dose to meet HbA1c and FBG targets remains suboptimal in the majority of T2D patients.

ObjectivesTo identify real-world, age-related trends in the use of insulin glargine 100 U/mL (Gla-100) as part of basal-supported oral therapy (BOT).Research design and methodsThe prospective, observational Titration and Optimization registry enrolled patients with poorly controlled type 2 diabetes mellitus initiated on Gla-100 BOT. The primary outcome was the proportion of patients with capillary fasting blood glucose (FBG) ≤110 mg/dL on ≥2 occasions and/or who met their individual HbA1c target within 12 months.Results2462 patients were analyzed (<65 years: n=1122; 65–74 years: n=771; ≥75 years: n=569). Diabetes duration (6.8, 8.9, and 11.2 years, p<0.0001) and proportion of women (40.7%, 47.9%, and 55.7%, p<0.0001) increased with age. Baseline HbA1c was highest in <65-year-olds (8.6% vs 8.4% and 8.5%, p<0.0001). Gla-100 up-titration until 12 months was highest in <65-year-olds (+11.6 U/day), compared with 65–74 (+10.2 U/day) and ≥75 years (+8.8; p<0.0001) but similar by units per kilogram, as was the decrease in FBG (<65: −64.1 mg/dL; 65–74: −56.1 mg/dL; ≥75: −53.4 mg/dL) and HbA1c (<65: −1.47%; 65–74: −1.31%; ≥75: −1.22%, p<0.0001). At 12 months, 65.9% of participants met the primary endpoint, with no significant difference between age groups. The proportion achieving their individual HbA1c target was lower for <65-year-olds (46.0% vs 54.3% and 54.7%; p<0.02). Symptomatic hypoglycemia incidence was more common in the ≥75-year-old group (3.4% vs 1.4% and 1.4%; p=0.0126).ConclusionsBOT with Gla-100 results in similar improvements of glycemic values with low risk of hypoglycemia across age groups. Given the link between HbA1c and long-term cardiovascular risk, ensuring appropriately stringent target-setting, intensification of basal insulin and making sure hypoglycemia is avoided is of paramount importance.Trial registration numberDatabase:https://awbdb.bfarm.de; Identifier: 1641; Date of registration: September 23, 2013

The aim of this study was to identify predictors of long-term response to the initiation of basal-supported oral therapy (BOT) with insulin glargine (IGlar-100). Patients from the observational TOP registry were grouped based on those who had achieved (responders) and those who had not achieved (non-responders) their HBA1c target and/or FBG <= 110 mg/dL 12 months after IGlar-100 initiation. Independent predictors of treatment response were identified by regression analysis. Data for 2444 patients were analysed (responders, n = 1610; non-responders, n = 834). Although the IGlar-100 dose increase over 12 months was larger for non-responders (+12.83 vs +9.46 U/d; P < 0.0001), the corresponding decrease in HbA1c was smaller (-0.88% vs -1.57%). Independent predictors of response included lower BMI (OR, 0.97; 95% CI, 0.95-1.00), lower FBG (OR, 0.98; 95% CI, 0.97-0.98) and HbA1c values at baseline (OR, 0.24; 95% CI, 0.18-0.31), a less ambitious HbA1c target (OR, 5.07; 95% CI, 3.37-7.63) and bedtime administration of IGlar-100 (OR, 1.55; 95% CI, 1.12-2.14). In conclusion, HbA1c was the clinically most significant baseline characteristic predictive of response to BOT. This may suggest an advantage of IGlar-100 initiation prior to excessive hyperglycaemia escalation.

Die IGLU-S-Studie untersuchte die Wirksamkeit von Insulinglulisin nach Wechsel des prandialen Insulins (Humaninsulin oder anderes kurzwirksames Insulinanalogon) bei Patienten mit Typ-1- (T1DM, + Basalinsulin) oder Typ-2-Diabetes (T2DM, + OAD oder Basalinsulin).

Lixisenatide has been studied extensively in randomized clinical trials; however, data on its use in the real-life practice are scarce. This study was a prospective, 26-week, multicenter, observational study conducted in Austrian diabetes centers and office-based practices to evaluate efficacy and safety of lixisenatide under real-life conditions in patients with type 2 diabetes. Out of 144 patients (mean BMI 36.4 kg/m2, disease duration 12.4 years), 113 completed the documentation at 6 months and 42% received basal insulin with or without oral antidiabetic drugs. The HbA1c declined from 8.7% (72 mmol/mol) to 7.9% (63 mmol/mol) and at study end 24.8% of the patients reached an HbA1c level below 7%. Fasting and postprandial glucose after lixisenatide administration were reduced by 27 ± 58 mg/dl and 45 ± 67 mg/dl, respectively. At study end body weight (− 4.5 ± 5.4 kg), triglycerides (− 10.8 ± 105 mg/dl), systolic blood pressure (− 4.8 ± 17.1 mmHg), and LDL cholesterol (− 3.7 ± 25 mg/dl) were reduced. The most commonly reported adverse events were gastrointestinal disorders (18.8%). Forty-three patients (30%) discontinued prematurely, mostly caused by lack of efficacy, occurrence of gastrointestinal disorders, and missing reimbursement. The average dose of insulin decreased slightly by 1.5 units (from 29.4 to 27.9). Lixisenatide demonstrated a similar efficacy and safety profile under real-life conditions as previously shown in randomized clinical trials. sanofi-aventis GmbH Austria.

Die IGLU-SIT-Studie untersuchte die Wirksamkeit von Insulinglulisin im Rahmen der Initiierung einer supplementären Insulintherapie (SIT) nach Versagen der oralen Therapie bei Typ-2-Diabetes-Patienten in der klinischen Praxis.