Administration Of Insulin Glargine Research Articles

Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes?

Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition. This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts. We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups. Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

Induction of Diabetes Mellitus Using Alloxan in Sprague Dawley Rats.

The use of rodent models for diabetes, particularly with pancreatic islet transplantation, has been prevalent in various preclinical trials. The purpose of this study is to establish a diabetes mellitus (DM) model in Sprague Dawley (SD) rats using alloxan evaluated by assessing alloxan dosage, the induction rate of diabetes, and glucose stability through insulin treatment. Over the course of 13 experimental rounds, diabetes was induced in 86 SD rats using alloxan at concentrations of 200 mg/kg (16 rats) or 150 mg/kg (70 rats). Various parameters, including diabetes induction rates, average insulin doses, extent of weight loss, and adverse effects such as diabetic ketoacidosis (DKA), were measured. The administration of 200 mg/kg of alloxan in rats resulted in severe diabetes induction, leading to DKA in three individuals, despite daily insulin glargine administration, DKA prevention was unsuccessful. The stability of alloxan decreases over time, especially when refrigeration is compromised during weighing. In the group treated with 150 mg/kg of alloxan, the diabetes induction rate was 83%. The average insulin dose was 2.21 units/kg/day. In contrast, the group treated with 200 mg/kg of alloxan exhibited a diabetes induction rate of 81% with a statistically significant higher average insulin requirement at 7.58 units/kg/day compared to 150 mg/kg of alloxan. Inducing diabetes in rats with 150 mg/kg of alloxan is considered more suitable for creating a diabetes model for xenogeneic islet transplantation compared to using 200 mg/kg of alloxan. This is due to fewer complications related to DKA or hyperglycemia and reduced need for exogenous insulin treatment.

Exercise and insulin glargine administration in mothers with diabetes during pregnancy ameliorate function of testis in offspring: Consequences on apelin-13 and its receptor

AimsDespite the evidence exhibited that diabetes during gestation (DDG) is linked with reproductive dysfunction in offspring, the underlying cellular mechanisms involved are not precisely defined. This study was designed to assess the impact of voluntary exercise and insulin glargine on DDG-induced metabolic and reproductive disorders in male offspring. Main methodsFifty female Wistar rats (three weeks old) received a control diet (n = 10) or high-fat-high-sucrose diet (to induce DDG; n = 40) for six weeks before breeding. From the 7th day of pregnancy onwards, blood glucose over 140 mg/dL was characterized as DDG. Then, the DDG animals were randomly divided into four subgroups with/without voluntary exercise and/or insulin glargine. To evaluate insulin resistance, a glucose tolerance test was performed on the 15th day of pregnancy. After three weeks, male offspring were weaned, and fed a control diet until 12 weeks old. At the end of the experiment, the lipid profile, sex hormones, and apelin-13 in the serum, mRNA expression of apelin receptors (APJ) in the testis and sperm analysis were assessed. Key findingsOur results indicated that voluntary exercise and/or insulin glargine administration in mothers with DDG ameliorated lipid profile, and sex hormones alterations, reduced the serum level of apelin-13, as well as increased APJ expression in testis, and quality of sperm in offspring. SignificanceCombined administration of voluntary exercise and insulin glargine during pregnancy by regulating of apelinergic system and inhibiting the metabolic and reproductive complications induced by DDG, can be considered as a suitable therapeutic strategy for improving sub-or in-fertility in the male offspring.

Comparative Analysis of PEG-Free and PEG-Based Self-Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides.

This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P octanol/water and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG-SEDDS in size, stability, and log D SEDDS/release medium. Oral IG bioavailability in PG/ZW-SEDDS and PEG-SEDDS is evaluated in rats. Among the various counterions studied, IG-BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW-SEDDS and PEG-SEDDS have similar ≈40nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50mM phosphate buffer pH 6.8. PG/ZW-SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG-SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG-free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.

Effect of Overlapping Insulin Glargine Administration in Decreasing Incidence of Hyperglycemia after Discontinuation of Intravenous Insulin Infusion

Effect of Overlapping Insulin Glargine Administration in Decreasing Incidence of Hyperglycemia after Discontinuation of Intravenous Insulin Infusion

Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration.

Metabolic diseases are a worldwide health problem. Insulin resistance (IR) is their distinctive hallmark. For their study, animal models that provide reliable information are necessary, permitting the analysis of the cluster of abnormalities that conform to it, its progression, and time-dependent molecular modifications. We aimed to develop an IR model by exogenous insulin administration. The effective dose of insulin glargine to generate hyperinsulinemia but without hypoglycemia was established. Then, two groups (control and insulin) of male Wistar rats of 100 g weight were formed. The selected dose (4 U/kg) was administered for 15, 30, 45, and 60 days. Zoometry, a glucose tolerance test, insulin response, IR, and the serum lipid profile were assessed. We evaluated insulin signaling, glycogenesis and lipogenesis, redox balance, and inflammation in the liver. Results showed an impairment of glucose tolerance, dyslipidemia, hyperinsulinemia, and peripheral and time-dependent selective IR. At the hepatic level, insulin signaling was impaired, resulting in reduced hepatic glycogen levels and triglyceride accumulation, an increase in the ROS level with MAPK-ERK1/2 response, and mild pro-oxidative microenvironmental sustained by MT, GSH, and GR activity. Hepatic IR coincides with additions in MAPK-p38, NF-κB, and zoometric changes. In conclusion, daily insulin glargine administration generated a progressive IR model. At the hepatic level, the IR was combined with oxidative conditions but without inflammation.

Evaluation of Early Insulin Glargine Administration in the Treatment of Pediatric Diabetic Ketoacidosis.

In the management of diabetic ketoacidosis (DKA), the standard of care is to administer insulin glargine after ketoacidosis has resolved and the patient is transitioning from intravenous (IV) insulin to subcutaneous insulin; however, there is evidence to suggest that earlier administration of insulin glargine may accelerate resolution of ketoacidosis. The objective of this research is to determine the efficacy of early subcutaneous insulin glargine on time to resolution of ketoacidosis in children with moderate to severe DKA. This retrospective chart review evaluated children age 2 to 21 years old admitted for moderate to severe DKA who received insulin glargine within 6 hours of hospital admission (early insulin glargine) compared with those who received insulin glargine greater than 6 hours from admission (late insulin glargine). The primary outcome was duration of time the patient received IV insulin. A total of 190 patients were included. The median time on IV insulin was lower in patients who received early insulin glargine compared with those who received late insulin glargine (17.0 [IQR, 14-22.8] vs 22.9 hours [IQR, 4.3-29.3]; p = 0.0006). Resolution of DKA was faster in patients who received early insulin glargine compared with those who received late insulin glargine (median, 13.0 [IQR, 9.8-16.8] vs 18.2 hours [IQR, 12.5-27.6]; p = 0.005). Length of pediatric intensive care unit (PICU) and hospital stay and incidences of hypoglycemia and hypokalemia were similar between the 2 groups. Children with moderate to severe DKA who received early insulin glargine had a significantly lower time on IV insulin, as well as significantly faster time to resolution of DKA when compared with those who received late insulin glargine. There were no significant differences observed in hospital stay and rates of hypoglycemia and hypokalemia.

A Randomized Controlled Trial on the Effect of Local Insulin Glargine on Venous Ulcer Healing

IntroductionTo determine whether the local administration of insulin glargine compared with placebo in nondiabetic patients with venous ulcers (VUs) leads to increased wound healing. MethodsA randomized controlled trial using a split-plot design was performed in 36 adults with leg VUs >25 cm2 and more than 3 mo of evolution. Each hemi-wound received either 10 UI insulin glargine or saline solution once a day for 7 d. Size of the wounds, thermal asymmetry, the number of blood vessels, and the percentage area of collagen content in wound biopsies were assessed at baseline and after 7 d of treatment. Blood capillary glucose was monitored once a day after the insulin injection. ResultsAfter 7 d of treatment, the hemi-wounds treated with insulin glargine were significantly smaller, had less thermal asymmetry, more blood vessels, and more collagen content than the saline-treated side. Correlation between thermal asymmetry and the number of blood vessels was also found (r2 = 66.2, P < 0.001). No patient presented capillary glucose levels ≤3.3 mmol/L nor any adverse effects. ConclusionsIn nondiabetic patients with chronic VUs, the topical administration of insulin glargine seems to be safe and promotes wound healing and tissue repair after 7 d of treatment.

Evaluation of Early Administration of Insulin Glargine in the Acute Management of Diabetic Ketoacidosis.

Few studies have evaluated the early use of insulin glargine in the management of diabetic ketoacidosis (DKA) patients. Early insulin glargine use in DKA was safe and associated with a trend towards faster DKA resolution. To evaluate the efficacy and safety of early insulin glargine administration for acute management of DKA in critically ill patients. This single-center retrospective cohort study included patients, who were >18 years of age with DKA, admitted to the intensive care unit (ICU) for at least 12 h, and received intravenous insulin infusion for at least 6 h. The primary endpoint was the association between the time to insulin glargine administration and time to DKA resolution. Linear and logistic regression analyses were performed. Of the 913 patients evaluated, 380 were included in the study. The overall mean age was 45±17 years, 196 (51.6%) were female, and 262 (70%) patients had type 1 diabetes mellitus. The mean blood glucose level was 584.9±210 mg/dL, pH was 7.16±0.17, anion gap was 28.17±6.9 mEq/L, and serum bicarbonate level was 11.19±5.72 mEq/L. Every 6-h delay in insulin glargine administration was associated with a 26-min increase in time to DKA resolution (95% confidence interval [CI], 14.76-37.44; p<0.0001), 3.2-h increase in insulin infusion duration (95% CI, 28.8-36; p<0.0001), and 6.5-h increase in ICU LOS (95% CI, 5.04-7.92; p<0.0001). Early administration of insulin glargine is potentially safe and may be associated with a reduction in time to DKA resolution and a shorter duration of insulin infusion.

Effects of exenatide on cardiac function, perfusion, and energetics in type 2 diabetic patients with cardiomyopathy: a randomized controlled trial against insulin glargine

BackgroundMultiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.Methods and resultsTwenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.ConclusionsT2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism.Trial registration NCT00766857

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.

Comment on Tang et al. Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. Diabetes Care 2015;38:1339–1346

Tang et al. (1) reported that the administration of insulin glargine, but not liraglutide, reduced the liver fat burden in patients with type 2 diabetes, whereas the improvement in the liver fat fraction was not significantly different from that in the liraglutide group in a 12-week randomized trial. This is an interesting clinical study on the effects of antihyperglycemic drugs on liver fat. However, there are some concerns about this study. First, given the different mechanisms by which insulin glargine and liraglutide therapies may reduce liver fat, the short observation period of 12 weeks may not be long enough to show the actual effects of the two agents, especially for liraglutide. …

Insulin glargine treatment of a ferret with diabetes mellitus

A 7.5-year-old spayed female ferret was evaluated because of weight loss despite a good appetite. Pancreatic insulinoma had been diagnosed at another animal hospital on the basis of detection of low blood glucose concentration on 1 occasion; however, concurrent determination of blood insulin concentration was not performed. The ferret had been treated SC with methylprednisolone acetate (unknown dosage) every 30 days for 2 years. No follow-up data regarding blood glucose concentration were available. On physical examination, the ferret was thin (weight, 0.619 kg [1.36 lb]) and bruised easily. Serum biochemical analysis revealed hyperglycemia (blood glucose concentration, 855 mg/dL; reference range, 63 to 134 mg/dL). Glucocorticoid injections were discontinued, and the ferret was administered prednisolone (1.13 mg/kg [0.51 mg/lb], q 12 h for 14 days, then 0.56 mg/kg [0.25 mg/lb], q 12 h for 7 days) orally. After prednisolone administration was discontinued, hyperglycemia and weight loss persisted. The ferret was administered insulin glargine (0.5 U) SC; blood glucose concentration was monitored every 2 hours for 24 hours, at which time the value had decreased to nearly within reference range. The owner continued insulin glargine administration at that dose every 12 hours; after 77 days of treatment, the ferret's weight was 0.731 kg (1.61 lb), which was considered normal, and blood glucose concentration was within reference range. Regular SC administration of insulin glargine was successful in the treatment of diabetes mellitus in the ferret of this report and may be effective for other diabetic ferrets.

Assessing insulin effectiveness at the end of the day: Once-daily versus twice-daily insulin glargine injection

Objective: Evidence supporting the twice-daily administration of insulin glargine as an approach to address its waning effectiveness at the end of a 24 hour period is sparse. We hypothesized that insulin concentrations determined during the last four hours of a 24 hour period would be greater when identical doses of insulin glargine were administered twice-daily as compared to once-daily among type 1 diabetes patients. Research Methods: Ten subjects with insulin deficient type 1 diabetes were admitted for two 38-hour studies at least one week apart. Patients received full-dose insulin glargine once daily at 0800 and half-dose insulin glargine twice-daily at 0800 and 2000 for at least one week in random order prior to overnight studies. Overnight glucose was stabilized with intravenous insulin on the evening prior to study, and subjects fasted and did not receive short acting insulin during the study period. Insulin concentrations were assessed every 30 minutes with an ultrasensitive assay between study hours 20 and 24. Results: Insulin concentrations for the final four hours of study period did not differ between once-daily and twice-daily insulin glargine administration (p = 0.38). Home glucose testing results and overnight plasma glucose concentrations did not differ between study conditions. Conclusions: These results demonstrate that insulin concentrations are equivalent during the last four hours of a 24-hour period when insulin glargine is administered once- or twice-daily. These findings do not support a role for twice-daily insulin glargine in the management of patients with type 1 diabetes.

Intravenous Overdose of Insulin Glargine without Prolonged Hypoglycemic Effects

BackgroundInsulin glargine is a long-acting insulin that can cause prolonged hypoglycemia when misdosed or overdosed subcutaneously. There are no reports of intravenous overdoses of insulin glargine. ObjectivesWe present a case of a patient inadvertently given a large intravenous dose of insulin glargine (100 units) who had an unremarkable course. Case ReportA 46-year-old woman with a history of type 2 diabetes was found to be hyperglycemic and was mistakenly given an intravenous bolus of 100 units of insulin glargine. She did not become hypoglycemic, did not require parenteral dextrose, and her blood sugar readings stabilized within 3 h. She was admitted and observed for 17 h and discharged without complication. ConclusionTo our knowledge, this is the first report of a significant intravenous insulin glargine administration. This patient had an unremarkable course and recovered without any parenteral glucose. This case, along with prior studies on healthy volunteers, suggests that unlike subcutaneous overdoses, intravenous insulin glargine misdose/overdose may not need prolonged observation; an observation time of 6 h may be sufficient in these patients.

Administration of insulin glargine thrice weekly by medical staff at a dialysis unit: a new insulin regimen for diabetic management in physically impaired patients undergoing hemodialysis

Diabetic patients undergoing hemodialysis may have difficulty in self-injecting insulin due to physical impairment or other disabilities. We hypothesized that postdialysis administration of insulin glargine by medical staff would improve diabetes care in this high-risk patient group. In this report, we describe six hemodialysis patients with type 2 diabetes and inadequate glycemic control who were admitted to our hospital. All patients had an inability to self-inject insulin due to visual impairment and/or stroke symptoms. Therefore, they had been unable to receive insulin treatment at the outpatient dialysis clinics within the last few months. After admission, the patients were administered insulin glargine after each hemodialysis session, thrice-weekly. Regarding glycemic control, blood glucose profiles including the circadian variation of 13-point blood glucose values for 48 h, hemoglobin A1C (HbA1C), and glycated albumin (GA) were evaluated before and after insulin treatment. Post-dialysis administration of insulin glargine significantly reduced blood glucose levels, particularly during the first 24 h after injection. HbA1C and GA levels were significantly decreased after 6 months, with no increase in the incidence of severe hypoglycemic episodes. Although further large controlled studies are needed, post-dialysis administration of insulin glargine by medical staff may improve glycemic control in physically impaired diabetic patients undergoing hemodialysis at outpatient clinics.

Response to Swinnen et al.

Response to Swinnen et al.

Glucose control in patients with type 2 diabetes based on frequency of insulin glargine administration

Glucose control and predictors of a switch from once to twice daily administration of insulin glargine in patients with type 2 diabetes was investigated. A mean decrease in %A1c of 0.52 ± 0.12 ( p = 0.14) resulted, indicating clinical relevance. Daily dose was the only significant predictor of twice daily therapy.

Perinatal Outcomes in Pregnancies Managed with Antenatal Insulin Glargine

We compared perinatal outcomes in pregnancies in which insulin glargine was used in the management of patients with pregnancies in which standard insulin therapy was used at a single institution. A retrospective analysis of 114 pregnant patients with diabetes (pregestational or gestational) managed at a single center between January 2004 and August 2006 was undertaken. Sixty-five patients managed with insulin glargine were compared with 49 patients managed with neutral protamine Hagedorn (NPH) insulin. Both groups were also treated with short-acting insulin (either regular, lispro, or aspart insulin). Maternal age, parity, prepregnancy weight, body mass index, duration of diabetes, hemoglobin A (1C) (at entry and final recorded) and gestational age at entry were similar for each group (glargine and NPH). Thirty patients had gestational diabetes (18 glargine and 12 NPH); there were no differences in numbers of patients in higher-order White's classification between the two groups. Cesarean section for obstetric reasons included labor abnormalities, malpresentation, fetal distress, and suspected macrosomia. There were no differences in gestational age at delivery, birth weight, preeclampsia, or frequency of cesarean section (total or for obstetric reasons). The frequency of shoulder dystocia was higher in the NPH group. Regarding neonatal outcomes, gestational age at delivery, birth weight, Apgar scores, admission to the neonatal intensive care unit, respiratory distress syndrome, hypoglycemia, and congenital anomalies were similar between the two groups. From this retrospective analysis, no adverse maternal or neonatal effects were seen from maternal administration of insulin glargine. A larger multicenter study is needed to confirm these findings. This preliminary report suggests that use of insulin glargine during pregnancy can be considered if maternal metabolic control is suboptimal using the standard split-mix regimen.

Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7–8% A1c levels. The TULIP study

To determine whether earlier administration of insulin glargine (glargine) vs. the intensification of lifestyle management (LM) improves glycaemic control in type 2 diabetes patients with A1c 7-8% treated with oral therapy. TULIP [Testing the Usefulness of gLargine when Initiated Promptly in type 2 diabetes mellitus (T2DM)] was a 9-month, 12-visit, open-label, multinational, multicentre, randomized study to evaluate starting glargine or intensifying LM in T2DM patients aged 40-75 years, body mass index (BMI) 24-35 kg/m2 and A1c 7-8%, treated with maximum doses of metformin and sulphonylurea for > or = 2 years. Glargine was injected once daily (evening) and titrated to fasting blood glucose 0.7-1.0 g/l. In the LM arm, dietary and physical activity counselling recommended stable weight for people with BMI < 27 kg/m2 or weight loss of 3 kg for patients with BMI > or = 27 kg/m2. A total of 215 patients were randomized to glargine (n = 106) or LM (n = 109). The primary objective was patients achieving A1c < 7% at endpoint. Secondary endpoints included changes in A1c, in fasting plasma glucose (FPG), body weight and hypoglycaemia incidence. Two hundred and eleven (52.6% male) patients were randomized and treated; mean (+/- s.d.) age 60.7 +/- 7.9 years, weight 84.5 +/- 13.1 kg, BMI 29.9 +/- 3.5 kg/m2 and A1c 7.6 +/- 0.4%. More patients reached A1c < 7% (66 vs. 38%; p < 0.0001) or < 6.5% (34 vs. 11%; p = 0.0001) with glargine vs. LM. The change in FPG from baseline to study endpoint was significantly greater in the glargine vs. the LM arm (-0.50 +/- 0.47 vs. -0.05 +/- 0.39 g/l respectively; p < 0.0001). Compared with the glargine group, the LM group showed a decrease in weight (+0.9 +/- 2.9 vs. -2.5 +/- 3.2 kg; p < 0.0001), as well as the expected lower symptomatic hypoglycaemia (55.3 vs. 25.0%; p < 0.0001) and nocturnal hypoglycaemia (20.4 vs. 5.6%; p = 0.0016). No significant changes were observed from baseline to study endpoint in any of the lipid parameters tested. In patients with T2DM with A1c 7-8%, who were previously treated by conventional LM and OAD therapy, adding glargine resulted in greater improvements in glycaemic control vs. intensifying LM.