Lower Rates Of Severe Hypoglycemia Research Articles

Glucagon prescribing and prevention of hospitalization for hypoglycemia in a large health system

AimsTo examine glucagon prescribing trends among patients at high risk of severe hypoglycemia and assess if a glucagon prescription is associated with lower rates of severe hypoglycemia requiring hospital care. MethodsRetrospective analysis of electronic health records from a large integrated healthcare system between May 2019 and August 2021. We included adults (≥18 years) with type 1 diabetes or with type 2 diabetes treated with short-acting insulin and/or recent history of hypoglycemia-related emergency department visit or hospitalization. We calculated rates of glucagon prescribing overall and by patient characteristics. We then matched 1:1 those who were and were not prescribed glucagon and assessed subsequent hypoglycemia-related hospitalization. ResultsOf 9,200 high risk adults, 2063 (22.4%) were prescribed glucagon. Among patients more likely to be prescribed glucagon were those younger, female, White, living in urban areas, with prior severe hypoglycemia, and with a recent endocrinology specialist visit. In the matched cohort (N = 1707 per arm), 62 prescribed glucagon and 33 not prescribed glucagon were hospitalized for hypoglycemia (adjusted incidence rate ratio 1.71, 95% CI 1.10–2.66; P = 0.018). ConclusionGlucagon prescribing was infrequent with significant racial and rural disparities. Patients with glucagon prescriptions did not have lower rates of hospitalization for hypoglycemia.

Continuous glucose monitoring versus blood glucose monitoring for risk of severe hypoglycaemia and diabetic ketoacidosis in children, adolescents, and young adults with type 1 diabetes: a population-based study

The effect of continuous glucose monitoring on the risk of severe hypoglycaemia and ketoacidosis in patients with diabetes is unclear. We investigated whether rates of acute diabetes complications are lower with continuous glucose monitoring, compared with blood glucose monitoring, and which metrics predict its risk in young patients with type 1 diabetes. In this population-based cohort study, patients were identified from 511 diabetes centres across Austria, Germany, Luxembourg, and Switzerland participating in the Diabetes Prospective Follow-up initiative. We included people with type 1 diabetes aged 1·5-25·0 years, with a diabetes duration of more than 1 year, who had been treated between Jan 1, 2014, and June 30, 2021, and had an observation time of longer than 120 days in the most recent treatment year. Severe hypoglycaemia and ketoacidosis rates during the most recent treatment year were examined in people using continuous glucose monitoring and in those using blood glucose monitoring. Adjustments of statistical models included age, sex, diabetes duration, migration background, insulin therapy (pump or injections), and treatment period. Rates of severe hypoglycaemia and diabetic ketoacidosis were evaluated by several continuous glucose monitoring metrics, including percentage of time below target glucose range (<3·9 mmol/L), glycaemic variability (measured as the coefficient of variation), and mean sensor glucose. Of 32 117 people with type 1 diabetes (median age 16·8 years [IQR 13·3-18·1], 17 056 [53·1%] males), 10 883 used continuous glucose monitoring (median 289 days per year), and 21 234 used blood glucose monitoring. People using continuous glucose monitoring had lower rates of severe hypoglycaemia than those using blood glucose monitoring (6·74 [95% CI 5·90-7·69] per 100 patient-years vs 8·84 [8·09-9·66] per 100 patient-years; incidence rate ratio 0·76 [95% CI 0·64-0·91]; p=0·0017) and diabetic ketoacidosis (3·72 [3·32-4·18] per 100 patient-years vs 7·29 [6·83-7·78] per 100 patient-years; 0·51 [0·44-0·59]; p<0·0001). Severe hypoglycaemia rates increased with percentage of time below target glucose range (incidence rate ratio 1·69 [95% CI 1·18-2·43]; p=0·0024, for 4·0-7·9% vs <4·0% and 2·38 [1·51-3·76]; p<0·0001, for ≥8·0% vs <4·0%) and glycaemic variability (coefficient of variation ≥36% vs <36%; incidence rate ratio 1·52 [95% CI 1·06-2·17]; p=0·022). Diabetic ketoacidosis rates increased with mean sensor glucose (incidence rate ratio 1·77 [95% CI 0·89-3·51], p=0·13, for 8·3-9·9 mmol/L vs <8·3 mmol/L; 3·56 [1·83-6·93], p<0·0001, for 10·0-11·6 mmol/L vs <8·3 mmol/L; and 8·66 [4·48-16·75], p<0·0001, for ≥11·7 mmol/L vs <8·3 mmol/L). These findings provide evidence that continuous glucose monitoring can reduce severe hypoglycaemia and ketoacidosis risk in young people with type 1 diabetes on insulin therapy. Continuous glucose monitoring metrics might help to identify those at risk for acute diabetes complications. German Center for Diabetes Research, German Federal Ministry of Education and Research, German Diabetes Association, and Robert Koch Institute.

COVID-19 Precautionary Measures and Type 1 Diabetes Patients in Saudi Arabia

AimTo minimize the spread of COVID-19, the Kingdom of Saudi Arabia (KSA) enforced a nationwide lockdown. We aimed to explore whether the manner in which Saudi patients with type 1 diabetes (T1D) manage their disease has changed during this unparalleled lockdown. MethodsAn online survey exploring the effect of lockdown on T1D outcomes was distributed among T1D patients residing in KSA during lockdown. ResultsA total of 1010 patients responded to the survey. Around 40% reported communicating with their physicians during lockdown. Age, level of education, residence, previous visits to diabetes education clinics, last HbA1c value, and average monthly income were all significantly associated with communication with the treating physician (p = 0.008, p < 0.001, p < 0.001, p = 0.002, p < 0.001, and p < 0.001, respectively). Age, level of education, and average monthly income were significantly associated with experiencing severe hypoglycemia (p = 0.036, p = 0.03, and p < 0.001, respectively), while average monthly income and level of education were significantly associated with experiencing diabetic ketoacidosis (DKA) (p < 0.001 and p = 0.0039, respectively); during lockdown. Patients who communicated with their physicians reported lower rates of severe hypoglycemia compared to those who did not (25.2% vs 30.7%, respectively). ConclusionAge and level of education were significantly associated with communication with the treating physician, and experiencing severe hypoglycemia and DKA; in patients with T1D during the lockdown period in Saudi Arabia. Keeping two-way virtual communication channels between physicians and their T1D patients should be encouraged.

PDB45 EVALUATING THE SHORT-TERM COST-UTILITY OF INSULIN DEGLUDEC VERSUS INSULIN GLARGINE U100 IN BASAL-BOLUS REGIMENS FOR TYPE 2 DIABETES IN CHINA

Insulin degludec (degludec) is an insulin analog with an ultra-long duration of action, low risk of hypoglycaemia and confirmed cardiovascular safety demonstrated in DEVOTE trial (NCT01959529). The study aimed to evaluate the short-term cost-utility of degludec versus insulin glargine 100 units/mL (glargine) for the treatment of type 2 diabetes (T2DM) receiving basal–bolus insulin therapy in China based on data from subgroup results of the DEVOTE trial. A short-term health economic model programmed in Microsoft Excel was conducted to compare costs in patients receiving once daily degludec or glargine over a 2-year time horizon. Clinical inputs and patient characteristics were taken exclusively from DEVOTE trial, whilst China-specific costs (the most current drug provincial biding price in china) were obtained from the literature. Both costs and health effects had not been discounted annually for such a short time horizon. Sensitivity analyses were conducted to assess the robustness of the results. Degludec was associated with a mean improvement of 0.00649 quality-adjusted life-years (QALYs) compared with glargine, with improvements driven predominantly by lower rates of severe hypoglycaemia with degludec versus glargine. degludec was associated with mean cost savings of 289.35 CNY per patient relative to glargine in patients with type 2 diabetes. Cost savings were primarily driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine. Insulin relative cost of degludec was 1040.36 CNY (16.98%) more than glargine. However, the costs of Non-fatal myocardial infarction, Non-fatal stroke, severe hypoglycaemia, and self-monitoring of blood glucose were reduced by 764.56 CNY (28.51%), 119.71 CNY (19.47%), 195.06 CNY (21.35%), and 210.13 CNY (36.94%), respectively. Sensitivity analyses demonstrated that the results were stable to variations in biding price. Among T2DM receiving basal–bolus insulin therapy in China, degludec is a cost saving treatment option compared with glargine.

Safety of Ramadan fasting in young patients with type1 diabetes: A systematic review and meta-analysis.

Aims/IntroductionAlthough patients with type 1 diabetes are medically exempt, many insist on fasting during Ramadan. Multiple daily insulin injections (MDI), premixed insulin and continuous subcutaneous insulin infusion (CSII) are commonly used. To date, little is known about the safety of Ramadan fasting in these patients.Materials and MethodsWe pooled data from 17 observational studies involving 1,699 patients treated with either CSII or non‐CSII (including premixed and MDI) regimen. The study outcomes were the frequencies of hypoglycemia, hyperglycemia and/or ketosis. Given the lack of patient‐level data, separate analyses for premixed and MDI regimen were not carried out.ResultsThe CSII‐treated group (n = 203) was older (22.9 ± 6.9 vs 17.8 ± 4.0 years), and had longer diabetes duration (116.7 ± 66.5 vs 74.8 ± 59.2 months) and lower glycated hemoglobin (7.8 ± 1.1% vs 9.1 ± 2.0%) at baseline than the non‐CSII‐treated group (n = 1,496). The non‐CSII‐treated group had less non‐severe hypoglycemia than the CSII‐treated group (22%, 95% CI 13–34 vs 35%, 95% CI 17–55). Of the non‐CSII‐treated group, 7.1% (95% CI 5.8–8.5) developed severe hypoglycemia, but none from the CSII‐treated group did. The non‐CSII‐treated group was more likely to develop hyperglycemia (12%, 95% CI 3–25 vs 8.8%, 95% CI 0–31) and ketosis (2.5%, 95% CI 1.0–4.6 vs 1.6%, 95% CI 0.1–4.7), and discontinue fasting (55%, 95% CI 34–76 vs 31%, 95% CI 9–60) than the CSII‐treated group.Conclusions The CSII regimen had lower rates of severe hypoglycemia and hyperglycemia/ketosis, but a higher rate of non‐severe hyperglycemia than premixed/MDI regimens. These suggest that appropriate patient selection with regular, supervised fine‐tuning of the basal insulin rate with intensive glucose monitoring might mitigate the residual hypoglycemia risk during Ramadan.

Rates of Hypoglycemia Predicted in Patients with Type 2 Diabetes on Insulin Glargine 300 U/ml Versus First- and Second-Generation Basal Insulin Analogs: The Real-World LIGHTNING Study.

IntroductionThe LIGHTNING study applied conventional and advanced analytic approaches to model, predict, and compare hypoglycemia rates of people with type 2 diabetes (T2DM) on insulin glargine 300 U/ml (Gla-300) with those on first-generation (insulin glargine 100 U/ml [Gla-100]; insulin detemir [IDet]) or second-generation (insulin degludec [IDeg]) basal-insulin (BI) analogs, utilizing a large real-world database.MethodsData were collected between 1 January 2007 and 31 March 2017 from the Optum Humedica US electronic health records [EHR] database. Patient-treatments, the period during which a patient used a specific BI, were analyzed for patients who switched from a prior BI or those who newly initiated BI therapy. Data were analyzed using two approaches: propensity score matching (PSM) and a predictive modeling approach using machine learning.ResultsA total of 831,456 patients with T2DM receiving BI were included from the EHR data set. Following selection, 198,198 patient-treatments were available for predictive modeling. The analysis showed that rates of severe hypoglycemia (using a modified definition) were approximately 50% lower with Gla-300 than with Gla-100 or IDet in insulin-naïve individuals, and 30% lower versus IDet in BI switchers (all p < 0.05). Similar rates of severe hypoglycemia were predicted for Gla-300 and IDeg, regardless of prior insulin experience. Similar results to those observed in the overall cohorts were seen in analyses across subgroups at a particularly high risk of hypoglycemia.PSM (performed on 157,573 patient-treatments) revealed comparable reductions in HbA1c with Gla-300 versus first- and second-generation BI analogs, alongside lower rates of severe hypoglycemia with Gla-300 versus first-generation BI analogs (p < 0.05) and similar rates versus IDeg in insulin-naïve and BI-switcher cohorts.ConclusionsBased on real-world data, predicted rates of severe hypoglycemia with Gla-300 tended to be lower versus first-generation BI analogs and similar versus IDeg in a wide spectrum of patients with T2DM.FundingSanofi, Paris, France.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0568-8) contains supplementary material, which is available to authorized users.

Cardiovascular Outcomes Trials Update: Insights from the DEVOTE Trial.

The DEVOTE study compared the cardiovascular safety of two basal insulins, degludec, and glargine U100 in patients with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). In this review, we summarize the results of DEVOTE and provide a clinical perspective. DEVOTE was a phase 3b, multicenter, international, treat-to-target, double-blind, event-driven trial. Patients with T2D > 50years of age with prior CVD or > 60years of age with CVD risk factors were randomly assigned to receive either degludec (n= 3818) or insulin glargine U100 (n= 3819) and were followed until at least 633 positively adjudicated major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) accrued. At baseline, the mean age of the subjects was 65.0years, the mean duration of diabetes was 16.4years, and the mean HbA1c was 8.4 ± 1.7%. After a median follow-up of 2years, HbA1c had decreased to 7.5 ± 1.2% in each group. Degludec was non-inferior to insulin glargine U100 with respect to the primary MACE outcome (hazard ratio 0.91; 95% CI 0.78-1.06). Significantly, lower rates of severe hypoglycemia and nocturnal severe hypoglycemia were observed with degludec compared to glargine U100 (rate ratios of 0.60; 95% CI 0.48-0.76 and 0.47; 95% CI 0.31 to 0.73, respectively). DEVOTE demonstrated that the cardiovascular safety of degludec was comparable to that of insulin glargine U100 in patients with T2D at high risk for CVD. Additionally, degludec was superior to insulin glargine U100 with respect to the risk for severe hypoglycemia. These results suggest that degludec might be preferred in patients at risk for severe hypoglycemia, including the elderly, those with CVD and/or those with chronic kidney disease.

Similar or Lower Severe Hypoglycemia Rates with Insulin Glargine 300 U/mL (Gla-300) vs. Glargine 100 U/mL (Gla-100), Detemir (IDet), and Insulin Degludec (IDeg) in 112,626 People with Type 2 Diabetes Mellitus (T2DM)—Predictive Modeling Using Real-World Data—Lightning

Real-world U.S. electronic health record (EHR) data, representative of the general population and real-life practice, were used to predict hypoglycemia rates in people with T2DM prescribed basal insulin (BI) analogs. Hypoglycemic events during BI treatment, as recorded by physicians in EHR, including patients initiating BI (“insulin-naïve”) and switching between BIs (“switchers”), were collected between 01 April 2015 and 31 March 2017. Based on real-world data, a predictive model (implementing machine learning and controlling for &amp;gt;160 baseline demographic and clinical variables) was developed and validated for each drug-specific cohort (patients treated with specific BI). The models predict significantly lower rates of severe hypoglycemia in real-world use with Gla-300 vs. Gla-100 or IDet, irrespective of prior insulin use. In insulin-naïve patients, lower rates of severe hypoglycemia are predicted with Gla-300 vs. IDeg (p&amp;lt;0.05), an unexpected finding that warrants further investigation, whereas comparable rates are shown in switchers (Figure). In summary, using real-world data, these predictive modeling results show similar or significantly lower severe hypoglycemia rates with Gla-300 vs. other BI in people with T2DM. Disclosure J. Pettus: Advisory Panel; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; MannKind Corporation. Advisory Panel; Self; Insulet Corporation. Consultant; Self; Senseonics. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. F.L. Zhou: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Employee; Spouse/Partner; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Lexicon Pharmaceuticals, Inc. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. R. Berria: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Jimenez: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I. Hramiak: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company. Advisory Panel; Self; GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Roche Pharma, Insulet Corporation, Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Merck &amp; Co., Inc.. Research Support; Self; Merck &amp; Co., Inc.. Speaker's Bureau; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association.

DEVOTE 5: Evaluating the Short-Term Cost-Utility of Insulin Degludec Versus Insulin Glargine U100 in Basal-Bolus Regimens for Type 2 Diabetes in the UK.

IntroductionThe aim of this study was to evaluate the short-term cost-utility of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) for the treatment of type 2 diabetes in the basal–bolus subgroup of the head-to-head cardiovascular (CV) outcome trial, DEVOTE.MethodsA cost-utility analysis was conducted over a 2-year time horizon using a decision analytic model to compare costs in patients receiving once daily degludec or glargine U100, both as part of a basal–bolus regimen, in addition to standard care. Clinical outcomes and patient characteristics were taken exclusively from DEVOTE, whilst health-related quality of life utilities and UK-specific costs (expressed in 2016 GBP) were obtained from the literature. The analysis was conducted from the perspective of the National Health Service.ResultsDegludec was associated with mean cost savings of GBP 28.78 per patient relative to glargine U100 in patients with type 2 diabetes at high CV risk. Cost savings were driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine U100. Degludec was associated with a mean improvement of 0.0064 quality-adjusted life-years (QALYs) compared with glargine U100, with improvements driven predominantly by lower rates of severe hypoglycemia with degludec versus glargine U100. Improvements in quality-adjusted life expectancy combined with cost neutrality resulted in degludec being dominant over glargine U100. Sensitivity analyses demonstrated that the incremental cost-utility ratio was stable to variations in the majority of model inputs.ConclusionThe present short-term modeling analysis found that for the basal–bolus subgroup of patients in DEVOTE, with a high risk of CV events, degludec was cost neutral (no additional costs) compared with glargine U100 over a 2-year time horizon in the UK setting. Furthermore, there were QALY gains with degludec, particularly due to the reduction in the risk of severe hypoglycemia.FundingNovo Nordisk A/S.Trial RegistrationClinicalTrials.gov identifier, NCT01959529.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0430-4) contains supplementary material, which is available to authorized users.

Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes

Insulin pump therapy may improve metabolic control in young patients with type 1 diabetes, but the association with short-term diabetes complications is unclear. To determine whether rates of severe hypoglycemia and diabetic ketoacidosis are lower with insulin pump therapy compared with insulin injection therapy in children, adolescents, and young adults with type 1 diabetes. Population-based cohort study conducted between January 2011 and December 2015 in 446 diabetes centers participating in the Diabetes Prospective Follow-up Initiative in Germany, Austria, and Luxembourg. Patients with type 1 diabetes younger than 20 years and diabetes duration of more than 1 year were identified. Propensity score matching and inverse probability of treatment weighting analyses with age, sex, diabetes duration, migration background (defined as place of birth outside of Germany or Austria), body mass index, and glycated hemoglobin as covariates were used to account for relevant confounders. Type 1 diabetes treated with insulin pump therapy or with multiple (≥4) daily insulin injections. Primary outcomes were rates of severe hypoglycemia and diabetic ketoacidosis during the most recent treatment year. Secondary outcomes included glycated hemoglobin levels, insulin dose, and body mass index. Of 30 579 patients (mean age, 14.1 years [SD, 4.0]; 53% male), 14 119 used pump therapy (median duration, 3.7 years) and 16 460 used insulin injections (median duration, 3.6 years). Patients using pump therapy (n = 9814) were matched with 9814 patients using injection therapy. Pump therapy, compared with injection therapy, was associated with lower rates of severe hypoglycemia (9.55 vs 13.97 per 100 patient-years; difference, -4.42 [95% CI, -6.15 to -2.69]; P < .001) and diabetic ketoacidosis (3.64 vs 4.26 per 100 patient-years; difference, -0.63 [95% CI, -1.24 to -0.02]; P = .04). Glycated hemoglobin levels were lower with pump therapy than with injection therapy (8.04% vs 8.22%; difference, -0.18 [95% CI, -0.22 to -0.13], P < .001). Total daily insulin doses were lower for pump therapy compared with injection therapy (0.84 U/kg vs 0.98 U/kg; difference, -0.14 [-0.15 to -0.13], P < .001). There was no significant difference in body mass index between both treatment regimens. Similar results were obtained after propensity score inverse probability of treatment weighting analyses in the entire cohort. Among young patients with type 1 diabetes, insulin pump therapy, compared with insulin injection therapy, was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the most recent year of therapy. These findings provide evidence for improved clinical outcomes associated with insulin pump therapy compared with injection therapy in children, adolescents, and young adults with type 1 diabetes.

Devoting attention to glucose variability and hypoglycaemia in type 2 diabetes.

In the Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE), insulin degludec was non-inferior to insulin glargine in terms of cardiovascular events and mortality. However, there were lower rates of severe hypoglycaemia with insulin degludec. DEVOTE investigators now extend these findings by presenting the results of two observational epidemiological analyses based on trial data. In the first of these analyses (DEVOTE 2), Zinman et al (Diabetologia DOI: 10.1007/s00125-017-4423-z ) demonstrate that, compared with individuals with lower day-to-day fasting glycaemic variability, those with higher day-to-day fasting glycaemic variability had a similar risk of major adverse cardiovascular events (MACE) but a higher risk of severe hypoglycaemia and all-cause mortality. In the second analysis (DEVOTE 3), Pieber et al (Diabetologia DOI: 10.1007/s00125-017-4422-0 ) found that individuals who experienced severe hypoglycaemia had a similar risk of MACE compared with those who never experienced severe hypoglycaemia, but had a more than twofold higher risk of subsequent total mortality and cardiovascular disease (CVD) mortality. The strengths of these studies relate to the availability of high-quality prospective data on adjudicated severe hypoglycaemia, MACE and mortality events in a large number of high-risk insulin-treated individuals with type 2 diabetes. Limitations include the observational nature of the data and thus residual confounding remains possible. Furthermore, the short duration of the trial resulted in limited statistical power for some analyses. Therefore, whilst DEVOTE 2 and DEVOTE 3 raise awareness of the mortality risks associated with glucose variability and severe hypoglycaemia in high-risk, insulin-treated patients with type 2 diabetes, they cannot clarify causal relationships. Preventing severe hypoglycaemia in those with type 2 diabetes should already be a priority in clinical practice. However, findings from future clinical trials are needed to guide physicians on whether it is beneficial to target glucose variability, and risk for severe hypoglycaemia, to reduce the risks for CVD events and mortality in these individuals.

Short Term Efficacy and Safety of Insulin Glargine in Type 2 Diabetes Inadequately Controlled with Single or Two Oral Agents: A Prospective, Open Label Study.

Basal insulin is among the second line treatment options for Type 2 Diabetes Mellitus (T2DM). Efficacy and safety of basal insulin in patients of T2DM, uncontrolled with Oral Antidiabetic Agents (OAAs) remains understudied in the Indian setting. To assess the efficacy and safety of insulin glargine in patients with T2DM who have uncontrolled glycaemic levels despite single or two OAAs therapy. In this prospective, open label study, T2DM patients above 40 years of age, having inadequate glycaemic control [Glycosylated Haemoglobin (HbA1c) above 8% and/or fasting glucose level of 140 mg/dl and above] with single or two OAAs over three consecutive months were included. Dosing of insulin glargine was adjusted as per Fasting Blood Glucose (FBG) and Post Prandial Blood Glucose (PPBG) levels. Patients were followed for 12 weeks and data was analysed by comparing 12th week findings to baseline values. In 40 cases included in final analysis, mean age was 56.35 ± 6.77 years, 52.5% were females and mean body mass index was 26.96 ± 4.59 kg/m2. Compared to baseline, significant reduction in HbA1c, FBG and PPBG blood glucose (all p<0.05) was seen. HbA1c goal of < 7% was achieved in 37.5% cases. Systolic (p>0.05) and diastolic (p<0.05) blood pressures reduced at 12 weeks as compared to baseline. Increase in weight was modest with mean increase of 1.06 kg (p>0.05). Overall, 14 symptomatic hypoglycaemia events were observed with none being severe. Short term administration of insulin glargine is effective in reducing glycaemia and is safe with lower rates of severe hypoglycaemia. It can be considered in patients with uncontrolled T2DM on mono- or two- OAAs treatment.

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.Diabet. Med. 25, 245–254 (2008)

Continuous subcutaneous insulin infusion: short-term benefits apparent, long-term benefits speculative

Continuous subcutaneous insulin infusion (CSII) is increasingly used as a means of insulin delivery for those with type 1 diabetes, and has recently been endorsed by NICE for this purpose. CSII improves glycaemic control compared to other intensified insulin regimens, with a small decrease in HbA1C and mean blood glucose, and a larger reduction in glucose fluctuation. This improved control is not associated with an increased risk of hypoglycaemia and CSII probably results in significantly lower rates of severe hypoglycaemia. There is no evidence that those using CSII are at increased risk of diabetic ketoacidosis. CSII is uniquely associated with a small risk of application site infection. CSII has a positive impact on quality of life. There is much less evidence concerning the benefits of CSII in reducing microvascular or macrovascular complication rates. Small studies, mostly from the 1980s, show improvements in markers of early nephropathy, retinopathy progression and neuropathy, but the potential long-term impact of CSII has not been proven. Recently CSII has been used in the management of those Br J Diabetes Vasc Dis 2004;4:104—08 with type 2 diabetes but evidence is lacking with regard to the benefits of using it in this group.