Oral Antidiabetic Drugs Group Research Articles

Five-Year Follow-Up of Diabetic Complications and Geriatric Alterations in French Older Patients with Type 2 Diabetes According to Treatment Modalities: The Observational Prospective GERODIAB Cohort.

Little is known about clinical events occurring in older patients with type 2 diabetes mellitus according to their therapeutic modalities based on the prescription of insulin and/or oral antidiabetic drugs. The aim of this study was to compare the complications of diabetes and geriatric alterations that occurred according to three therapeutic modalities prescribed over 5 years. A total of 616 patients from the GERODIAB cohort (mean age 77.1 years) were divided into three groups: an insulin-only group (n = 200), a group receiving insulin and one or more oral antidiabetic drug (n = 169), and an oral antidiabetic drug group without insulin (n = 247). We compared the diabetic complications and geriatric alterations that occurred over 5 years in patients without these pre-existing complications. At inclusion, there was a significant difference between glycosylated hemoglobin values, and between the frequencies of most diabetic complications and geriatric alterations, with higher frequencies in the insulin group and lower frequencies in the oral antidiabetic drug group. At the end of the follow-up, there was still a significant difference between the mean glycosylated hemoglobin of the three groups (mean for all patients 7.4 ± 0.8%). The frequencies of new clinical events were high and they were generally higher in the insulin group. They were not significantly different between the three groups, with the exception of four events: heart failure, retinopathy, transfer to a nursing home (more frequent in the insulin group), and hypoglycemia (more frequent in the insulin + oral antidiabetic drug group). Some frequencies of the total diabetic complications (including complications at inclusion and at the follow-up) in the oral antidiabetic drug group were close to those in the insulin group, although only at inclusion. Mortality was higher in the insulin group and lower in the oral antidiabetic drug group. The increased frequency of hypoglycemia in the insulin + oral antidiabetic drug group raises doubts about the value of continuing a secretagogue drug when insulin is introduced. As the vast majority of patients were not yet receiving antidiabetic drugs with cardiovascular action, our results on heart failure could help in conducting specific studies on these drugs in older patients with type 2 diabetes.

POLA PENGGUNAAN OBAT ANTIDIABETES PADA PASIEN RAWAT INAP RSUD ANUTAPURA PALU

This study aims to determine the pattern of antidiabetic treatment and the accuracy of the use of antidiabetic drugs based on indications, drugs, patients, and doses of use at Anutapura Hospital Palu. This study is a descriptive research method using a cross-sectional method with retrospective data collection based on medical record data for type 2 Diabetes mellitus patients in 2021. Sampling was carried out using a minimized sampling technique with medical record data of 30 patients based on inclusion criteria. The results of this study are patients with Type 2 Diabetes Mellitus, which are female, as many as 16 patients (54%), in the age range of 48-60 years as many as 14 patients (46%), the most widely used oral antidiabetic drug group is Biguanid group (Metformin) as many as 18 patients (70%), the type of insulin drug that was most widely used was Novorapid as many as 13 patients (61.91%), and adjunctive drugs with the highest use of therapy, namely Amlodipine as many as 14 patients with a percentage (7, 4%). Antidiabetic treatment is based on the right indication (100%), right drug (50%), right patient (93%) and right dose (100%).

Real-world Data of Glycemic Control in a Suburban Population in Northern India during the COVID-19 Pandemic

Abstract Background: This study compared the 2-year glycemic outcomes with oral antidiabetic drugs (OADs) versus combination of OADs with insulin among the real-world patients at a single suburban center in India during the COVID-19 pandemic. Methods: Patients aged >18 years on the treatment for type 2 diabetes mellitus were included and followed up for 2 years. The patients were divided into four groups according to their antidiabetic medication as follows: (1) sodium-glucose cotransporter-2 inhibitors (SGLT2i) + insulin + OADs; (2) SGLT2i + OADs; (3) insulin + OADs (excluding SGLT2i); and (4) OADs excluding SGLT2i. Patients who were reluctant to initiate insulin as add-on therapy or those already taking insulin but wanting to switch to OADs were prescribed SGLT2i as add-on therapy. The parameters measured at every follow-up were blood pressure, weight, fasting blood sugar (FBS), postprandial blood sugar, and HbA1c. Results: In all, 1204 patients were included in the study. The mean age of patients was 59.07 ± 13.08 years, and 729 (60.54%) were males. Out of 1204 patients, the HbA1c data were available for only 472 patients. All glycemic parameters were maintained in the SGLT2i + Insulin + OADs group over the period of 3 years with no significant change in their values. The number of patients in the SGLT2i + OADs group more than doubled over the 2 years of follow-up. There was a significant improvement in weight and FBS at year 2 in this group. A significant improvement in HbA1c and FBS was seen in patients with baseline HbA1c ≥10 at baseline. No statistically significant change was observed in any of the clinical parameters in patients in the Insulin + OADs (excluding SGLT2i) group. Only about 50% of those who were on insulin at baseline, continued insulin at the first and second follow-up. In the OADs (excluding SGLT2i) group, weight and post lunch blood sugar showed a significant decrease at the second follow-up. Among patients who remained on OADs throughout the study, there was a significant improvement in HbA1c from baseline at year 2, although other parameters did not show any significant improvement. Conclusion: Patients on various OAD regimens showed better glycemic control compared to those on combined insulin and OADs in this study in a suburban population in India.

Insulin Therapy Increases the Risk of Hypokalemia and Arrhythmia in Diabetic Patients with Coronary Heart Disease: A Retrospective Study in Wahidin Sudirohusodo General Hospital

Background: Cardiovascular disease is the most common cause of morbidity and mortality in diabetic patients. Patients with Diabetes Mellitus (DM) often require insulin therapy to control hyperglycemia, yet, it is associated with the risk of hypokalemia and dysrhythmia. Objectives: To evaluate the prevalence and the risk of hypokalemia and arrhythmia due to insulin therapy in DM patients with Coronary Heart Disease (CHD) comorbidity. Material and Methods: The study was conducted retrospectively based on medical record data from January 2021 to December 2021 in Wahidin Sudirohusodo general hospital. The inclusion criteria include the out-hospital patients diagnosed with DM with CHD comorbidity. The patients were divided into 2 groups, those who received insulin and those who received oral antidiabetic drugs (OAD). Hypokalemia was defined if an electrolyte characterized by a low serum potassium concentration with a normal range of 3.5 – 5.0 mEq/L. Arrhythmia was defined if abnormal changes in a regular heartbeat, including an irregular heartbeat, a skipped heartbeat, a fast heart rate (tachycardia), or a slow heart rate (bradycardia). Results: The data were obtained from 322 patients’ medical record, 161 was treated with insulin, and 161 received OAD. The insulin-treated patients had a significantly lower blood potassium level compared to the OAD group. The insulin group had 63,40% incidents of hypokalemia, while in the OAD group only 16,80% experienced hypokalemia (p<0.05). The presence of arrhythmia was detected in 63,40 % of insulin-treated patients, while only 29,80% had arrhythmia in the OAD group (p<0,05). Conclusions: Insulin Therapy in DM patients with coronary heart disease can increase the incidence of hypokalemia, which may result in arrhythmia in patients with coronary heart disease.

Effect of sodium–glucose cotransporter 2 inhibitor medication on new prescriptions of antihypertensives, antigout/antihyperuricemics and antidyslipidemics in Japan: Analysis using the JMDC Claims Database

This study aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on new prescriptions of drugs, including antihypertensives, antigout/antihyperuricemics and antidyslipidemics, for the treatment of lifestyle-related diseases in Japanese patients with diabetes mellitus using the JMDC Claims Database. Patients with type 2 diabetes mellitus who were newly treated with SGLT2i or other oral antidiabetic drugs and had not been prescribed any antihypertensives, antigout/antihyperuricemics or antidyslipidemics for at least 1 year were extracted from the database. Using propensity score calibration matching (1:1), we assessed the proportion of patients who started the aforementioned concomitant medications within 2 years, and the risk ratio of SGLT2i to other antidiabetic medication groups was calculated. In 856,796 patients with diabetes mellitus, 734, 1,197 and 703 propensity score calibration-matched patients in each group were analyzed for the prescription of antihypertensives, antigout/antihyperuricemics and antidyslipidemics, respectively. The new prescriptions of antihypertensives and antigout/antihyperuricemics were lower in the SGLT2i group than those in the other oral antidiabetic drug group (risk ratio 0.66 and 0.37, respectively), whereas those of antidyslipidemics were more common in the SGLT2i group (risk ratio 1.43). New prescriptions of antihypertensives or antigout/antihyperuricemics were lower for patients taking SGLT2i than those taking other oral antidiabetic drugs, probably due to a reduction of blood pressure and uric acid levels by SGLT2i. The more frequent prescriptions of antidyslipidemics might partially reflect a moderate increase in low-density lipoprotein cholesterol levels as a result of sodium-glucose cotransporter 2 inhibition.

Proportional relationship between periodontal inflamed surface area, clinical attachment loss, and glycated hemoglobin level in patients with type 2 diabetes mellitus on insulin therapy and on oral antidiabetic therapy.

Treatment of diabetes includes oral antidiabetic drugs (OAD), insulin, or their combinations. Insulin can achieve faster glycemic control and have anabolic action on bone. This study was undertaken to assess the prevalence and severity of periodontitis, and to estimate the proportional relationship between periodontal inflamed surface area, clinical attachment loss, and glycated hemoglobin (HbA1c) level in patients with type 2 diabetes (T2DM) on OAD therapy and on insulin therapy. This cross-sectional study comprised 130 patients with T2DM on OAD therapy (OAD group) and 130 patients with T2DM on insulin therapy (INSULIN group). All patients were assessed for sociodemographic, behavioral characteristics, clinical history, periodontal parameters (bleeding on probing, probing depth, clinical attachment loss [Clinical AL], Oral Hygiene Index-simplified, plaque index, and periodontal inflamed surface area [PISA]), and biochemical variables (HbA1c, fasting plasma glucose, postprandial plasma glucose). Prevalence, extent, and severity of periodontitis and PISA were lower in the INSULIN group as compared with the OAD group. A proportional relationship was observed between HbA1c and PISA and between HbA1c and Clinical AL. A unit increase in HbA1c is associated with an increase in PISA of 130.47mm2 and an increase in Clinical AL of 0.182mm. A proportional relationship was observed between PISA, clinical attachment loss, and HbA1c level in patients with type 2 diabetes mellitus on insulin therapy and OAD therapy. Despite comparable oral hygiene status and glycemic control between the two groups, the periodontal parameters were lesser in the INSULIN group as compared with the OAD group.

Is the insulin necessary for the struggle against oxidative stress in diabetes mellitus type 2: A pilot study

Background/Aim. Hyperglycaemia has a detrimental effect on the progress of micro/macrovascular complications in patients with diabetes mellitus type 2 (T2DM). Additionally, all known complications in T2DM are coupled with oxidative stress developed from different metabolic pathways. The aim of this study was to estimate the quality of glucoregulation and the degree of oxidative stress in T2DM patients depending on the applied therapeutic protocol and assess their correlation with clinical data and crucial biochemical parameters important for the development of diabetes complications. Methods. All included patients were divided into two groups: those treated with oral antidiabetic drugs (OAD) and those treated with oral antidiabetic drugs and insulin (OA-DINS). Thiobarbituric acid reactive substances (TBARS), total sulfhydryl groups (TSH), the activity of superoxide dismutase (SOD), total nitrites (NOx), vascular endothelial growth factor (VEGF), and activities of matrix metalloproteinase 9 (MMP9) were measured, together with lipid profile and routine biochemical parameters. All subjects were analyzed for demographic characteristics and detailed medical history as well as smoking habits and calculated for body mass index (BMI). Results. All patients were uniformly poor glucoregulated and dyslipidemic. SOD activity was decreased, and lipid peroxidation was increased in the OAD group compared to OADINS. Deficient glucoregulation in both the OAD and the OADINS groups did not associate with an oxidative state outcome. In both of these groups, the concentrations of VEGF and MMP9 were significantly higher than in controls. Conclusion. The better antioxidative outcome, expressed with a normalized concentration of TBARS, preserved TSH, and normalized SOD activity in T2DM patients treated with OADINS compared to those treated exclusively with OAD, suggests the need for more careful consideration of earlier insulin introduction into T2DM therapy in order to prevent the development of complications.

Relationship between the early initiation of insulin treatment and diabetic complications in patients newly diagnosed with type 2 diabetes mellitus in Korea: A nationwide cohort study.

Aims/IntroductionTo evaluate the relationship between early insulin initiation within a year after type 2 diabetes mellitus diagnosis and the risk of diabetic complications.Materials and methodsWe carried out a cohort study using the Korean National Health Insurance Service database. The study participants were newly diagnosed with type 2 diabetes mellitus between 2009 and 2013. After applying propensity score matching (1:1) to the cohort of patients who received two or more oral antidiabetic drugs (OADs) or insulin as the first prescription within 1 year after type 2 diabetes mellitus diagnosis, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) using a Cox proportional hazards regression to compare the risk of diabetes‐related microvascular and macrovascular complications and all‐cause mortality in insulin versus OAD initiators.ResultsWithin the cohort, 52,188 and 1,804 patients received OAD and insulin, respectively. After matching, each group contained 534 patients. Compared with the OAD group, the risk of overall microvascular complications was significantly higher for insulin (HR 1.48, 95% CI 1.28–1.71). No increased risks of overall macrovascular complications (HR 0.90, 95% CI 0.62–1.30) and all‐cause mortality were observed (HR 1.06, 95% CI 0.67–1.68).ConclusionsIn the present study, early insulin treatment was not associated with the risk of macrovascular complications and all‐cause mortality compared with OAD treatment; however, the risk of microvascular complications was higher in the insulin group.

Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add-on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA-PRIME).

AimTo compare (in the LIRA‐PRIME [NCT02730377], a randomized open‐label trial), the efficacy of liraglutide in controlling glycaemia versus an oral antidiabetic drug (OAD) in patients with uncontrolled type 2 diabetes (T2D), despite metformin use in a primary care setting (n = 219 sites, n = 9 countries).Materials and MethodsAdults (n = 1991) with T2D (HbA1c 7.5%‐9.0%) receiving metformin were randomized 1:1 to liraglutide (≤1.8 mg/d) or one OAD, selected by the investigator, added to metformin, for up to 104 weeks. Primary endpoint: time to inadequate glycaemic control (HbA1c > 7.0%) at two scheduled consecutive visits after week 26. Outcomes were assessed for liraglutide versus a pooled OAD group, and (post hoc) liraglutide versus sodium‐glucose co‐transporter‐2 inhibitors, dipeptidyl peptidase‐4 inhibitors, and sulphonylureas individually.ResultsAmong randomized patients (liraglutide, n = 996; OAD, n = 995), 47.6% were female, mean age was 57.4 years and mean HbA1c was 8.2%. Median time to inadequate glycaemic control was 44 weeks longer with liraglutide versus OAD (109 weeks [25% percentile, 38; 75% percentile, not available] vs. 65 weeks [25% percentile, 35; 75% percentile, 107], P < .0001). Changes in HbA1c and body weight at week 104 or at premature treatment discontinuation significantly favoured liraglutide over OAD. Hypoglycaemia rates were comparable between groups and few patients discontinued because of adverse events (liraglutide, 7.9% [n = 79]; OAD, 4.1% [n = 41]). Similar results were observed in the post hoc analysis for liraglutide versus individual OAD classes.ConclusionsGlycaemic control was better maintained with liraglutide versus OAD, supporting liraglutide use when intensifying therapy in primary care patients with T2D.

1507-P: Dose–Response Relationship between Periodontal Inflamed Surface Area and Glycated Haemoglobin Level in Patients with Type 2 Diabetes Mellitus on Insulin Therapy and on Oral Antidiabetic Therapy

A bidirectional inflammatory link exists between periodontitis and diabetes mellitus. Diabetes increases the prevalence and severity of periodontitis and periodontitis affects glycemic control. Treatment of diabetes is with oral antidiabetic drugs (OAD), insulin or their combinations. Insulin achieves faster glycemic control and has other beneficial effects. This study was undertaken to compare the prevalence, extent and severity of periodontal disease, to correlate periodontal inflamed surface area (PISA) with Glycated Hb (HbA1c) and to find the dose response relationship between PISA and HbAic in type 2 diabetes mellitus (T2DM) on insulin therapy and on OAD therapy. The study comprised of 130 T2DM patients on oral antidiabetic drugs therapy (OAD group) and 130 T2DM patients on insulin therapy (INSULIN group). All subjects were assessed for periodontal parameters (BOP, PPD, CAL, OHI-S Index, PI Index and PISA) and systemic parameters (HbA1c, FPG, PPG). The proportion of periodontitis was lower in INSULIN group (46.2%) as compared to OAD group (83.1%). Extent and severity of periodontitis and PISA were lower in INSULIN group as compared to OAD group. HbA1c was positively correlated with PISA in OAD group(r=0.391)(p &amp;lt;0.001) and in INSULIN group (r=0.492) (p &amp;lt;0.001). A dose response relationship between PISA and HbA1c has been observed and an increase in HbA1c of 1% is associated with an increase in PISA of 195mm2 (p &amp;lt;0.001). Multiple linear regression models showed that shifting from OAD to INSULIN results in the decrease of PISA by 605.4mm² (p &amp;lt;0.001). This indicates to the beneficial effects of insulin on periodontal tissues. Dose response relationship between HbA1c and PISA confirm the bidirectional relationship between diabetes mellitus and periodontal disease. Disclosure R.J. Vadakkekuttical: None. S. Pattayil: None. C. Radhakrishnan: None.

Effect of basal insulin supplement therapy on diabetic retinopathy in short‐duration type 2 diabetes: A one‐year randomized parallel‐group trial

BackgroundIn this study, we compared the effect on diabetic retinopathy (DR) between oral antidiabetic drugs (OADs) alone and in combination with basal insulin‐supported OADs therapy (BOT). [Correction added on 11 November 2019, after first online publication: In under Background section, “DR” has been corrected into “diabetic retinopathy (DR)”.]MethodsBetween January 2015 and January 2018, this study enrolled 290 patients (age 18‐65 years) with diabetes duration between 0 and 5 years. Patients were randomly assigned to receive OADs or BOT after 14 days intensive insulin treatment. Examinations were performed at the beginning and end of the study.ResultsFewer patients developed DR in the BOT than OADs group (8 [6.06%] vs 12 [8.3%], respectively), and all cases of DR were non‐proliferative. Blood glucose concentrations were higher in the BOT than OADs group at the 3rd month, but lower in the former at the 6th and 12th month. The rate of reaching target HbA1c ≤7% was lower in the BOT than OADs group at the 3rd month (63.6% vs 72.2%, respectively), similar between the two groups at the 6th month (60.6% vs 66.6%, respectively) and higher in the BOT group at the 12th month (75.0% vs 61.1%, respectively). The SD of fasting blood glucose (FBG), coefficient of variation of FBG, SD of blood glucose (SDBG), and mean amplitude of glycemic excursions were lower in the BOT than OADs group. Changes in the levels of three cytokines (interleukin [IL]‐1β, IL‐6, and IL‐17α) were significantly less in the BOT than OADs group.ConclusionsTwelve months of BOT decreased the incidence of DR in short‐duration type 2 diabetes by reducing glycemia more effectively, stably, and completely than OADs alone.

PDB8 - HBA1C As A Risk Factor For Cardiovascular Disease in Type 2 Diabetes Mellitus: A Hospital-Based Study in Taiwan

Cardiovascular disease (CVD) is the major cause for death in type 2 diabetes mellitus (T2DM) patients worldwide. Evidence has emerged that HbA1c may increase the risk for CVD and others. This study was to examine the relationship between HbA1c and onset cardiovascular disease, and target HbA1c in T2DM patients in Taiwan. Data in T2DM patients were extracted from Chang Gung Memorial Hospital between 2007 and 2014. CV outcome events were derived post T2DM diagnosed with data in medical charts such as HbA1c until end of the year 2014. A total of 126,079 T2DM patients were enrolled into the analysis. Per 1% unit increase in baseline HbA1c and mean HbA1c, hazard ratio (HR) for CVD were 1.05 (95% CI: 1.04 ~ 1.06, p < 0.001) and 1.31 (1.29 ~ 1.33, p < 0.001) when patients had previous CVD, respectively (p < 0.001). Per 1% unit increase in mean HbA1c, hazard of CVD increased 23% (17% ~ 29%), 21% (19% ~ 29%), and 6% (3% ~ 9%) for other treatment, oral anti-diabetic drug (OAD), and combination of insulin and OAD, respectively (all p < 0.001). Hazard of CVD increased more than 100% when mean HbA1c was higher than 8% compare with mean HbA1c was lower than 7% (p < 0.001). The rate of achieving target HbA1c level were significantly higher in OAD (1.45, 1.37 ~ 1.53) and lower in combination of insulin and OAD group (0.87, 0.82 ~ 0.93) when compared with the other treatment group (all p < 0.001). High HbA1c increases risk for CVD in T2DM patients revealed from large hospital based cohort in Taiwan. Maintenance of HbA1c control needs to be monitored continuously, especially in T2DM patients whose mean HbA1c was higher than 8%, with treatments in combination of insulin and OAD.

Effects of pioglitazonetreatment on blood leptin levels in patients with type2 diabetes.

Aims/IntroductionThe aim of the present study was to carry out a meta‐analysis of randomized controlled trials (RCTs) that investigated the effects of pioglitazone on blood leptin levels in patients with type 2 diabetes.Materials and MethodsLiterature searches were carried out using Medline, the Cochrane Controlled Trials Registry and ClinicalTrials.gov, and RCTs that investigated the effects of pioglitazone on blood leptin levels in patients with type 2 diabetes were selected. Standardized mean differences and 95% confidence intervals were calculated.ResultsA total of 10 RCTs met the eligibility criteria and were included in the meta‐analysis. Significantly lower blood leptin levels were observed in the pioglitazone group (standardized mean difference −0.58, 95% confidence interval −1.12 to −0.05%, P = 0.03) than in the placebo group. There was no significant difference in blood leptin levels observed between the pioglitazone and oral antidiabetic drug groups (standardized mean difference −0.01, 95% confidence interval −0.20 to 0.19%, P = 0.93).ConclusionsThere was a significant difference in blood leptin levels between the pioglitazone and placebo groups. However, relatively few RCTs were included in the study, and there was a high level of statistical heterogeneity; we believe that this could have affected the results.

Self-Monitoring of Blood Glucose to Assess Dawn Phenomenon in Chinese People with Type 2 Diabetes Mellitus.

Aims. We investigated whether self-monitoring of blood glucose could be used to assess dawn phenomenon in Chinese people with type 2 diabetes mellitus (T2DM). Methods. A total of 306 people with T2DM underwent continuous glucose monitoring and self-monitoring of blood glucose for 72 h. A linear model was used to fit the optimal linear formula of the magnitude of dawn phenomenon (ΔDawn) and self-monitoring of blood glucose values. Results. The prevalence of dawn phenomenon was similar within different oral antidiabetic drug groups (42.5%, 31.5%, and 40.9%, P = 0.216). Multiple variable linear regression showed that prebreakfast, prelunch, and predinner glucose measurements were independently and significantly correlated with ΔDawn. The linear formula between ΔDawn and blood glucose was as follows: ΔDawn (mg/dL) = 0.557 × prebreakfast − 0.065 × prelunch − 0.164 × predinner − 20.894 (mg/dL) (adjusted R2 = 0.302, P = 0.000). Conclusions. Dawn phenomenon could be partly assessed by blood glucose self-monitoring in Chinese people with T2DM using the abovementioned formula. The incidence of dawn phenomenon was similar among patients in different oral antidiabetic drug groups.

Cardiovascular safety of SGLT2 inhibitors

Sodium-glucose co-transporter-2 (SGLT2) inhibitors, also called flozins, are a new group of oral antidiabetic drugs. Due to progressive nature of type 2 diabetes and gradual deterioration of pancreatic beta cell function, achieving good diabetes control still remains a challenge. This stimulates researchers and clinicians to search for new directions in diabetes treatment and to develop optimal antidiabetic therapy. Particularly interesting in this context are (besides incretin-based therapies) SGLT2, because they reduce renal glucose reabsorption and, thereby, increase urinary glucose excretion. Their action is independent from an insulin, both in terms of an insulin secretion and action. Type 2 diabetes remains one of the major cardiovascular risk factors. The most important issue related to this group of drugs is therefore establishing the principles of safe, well-tolerated and effective long-term treatment of patients with vascular complications of various severity, including cardiovascular complications mainly. New antidiabetic drugs should not only improve glycaemic control, but also contribute to the reduction of cardiovascular morbidity and mortality.

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

AimType 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.MethodsData 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.ResultsThere 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).ConclusionLong-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.

Keeping Up With Safety Warnings of Oral Antidiabetic Drugs

Timothy Nguyen, PharmD, BCPS Oral antidiabetic drugs are no doubt major components in the management for patients with type 2 diabetes. Nurse practitioners (NPs), without exception, are frontline in the management of patients with diabetes. With so many new oral antidiabetic drugs available for diabetes management, new safety warnings on potential side effects associated with these agents also emerge. Oftentimes, it is difficult for practitioners to sort out and stay abreast with the new safety information in their busy practices. In this issue of the journal, a few important and unique safety profiles of the newer oral antidiabetic drug classes will be highlighted to help NPs sort out the safety information associated with their use. NPs are very familiar with older oral antidiabetic drugs such as alpha-glucosidase inhibitors, biguanides, sulfonylureas, meglitinide, and others; however, the relatively newer classes of oral antidiabetic drugs including thiazolidinediones, dipeptidyl peptidase-4 inhibitors (also known as “gliptins” or incretin enhancers), and sodium-glucose cotransporter 2 inhibitors have had more recent warnings released. Warnings issued from the Food and Drug Administration (FDA) regarding diabetes drugs involve cardiovascular-related risks. For those drugs that belong to the thiazolidinedione class (pioglitazone and rosiglitazone), in 2007 the FDA communicated a possible association between rosiglitazone and increased cardiovascular risk. According to the RECORD trial, those with type 2 diabetes who took either rosiglitazone plus other oral antidiabetic drugs were compared with those who took metformin and sulfonylureas. In the secondary composite end point, those in the rosiglitazone group showed an increase in heart failure. In light of cardiovascular warnings and in general, practitioners should probably avoid using this group of oral antidiabetic drugs in people with heart failure. A few years later,

Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52-week, open-label, parallel-group trial.

The safety and efficacy of liraglutide in combination with an oral antidiabetic drug (OAD) compared with combination of two OADs were assessed in Japanese patients with type 2 diabetes. This was a 52-week, open-label, parallel-group trial in which patients whose type2 diabetes was inadequately controlled with a single OAD (glinide, metformin, α-glucosidase inhibitor or thiazolidinedione) were randomized 2:1 to either pretrial OAD in combination with liraglutide 0.9mg/day (liraglutide group; n=240) or pretrial OAD in combination with an additional OAD (additional OAD group; n=120). The primary outcome measure was the incidence of adverse events (AEs). Overall, 86.3% of patients in the liraglutide group and 85.0% of patients in the additional OAD group experienced AEs; these were similar in nature and severity. Adverse event rates were 361 and 331 per 100patient-years of exposure, respectively. Confirmed hypoglycemia was rare (seven episodes in two patients on liraglutide, and two in two patients on additional OAD). There were no reported pancreatitis events, and no unexpected safety signals were identified. Mean reductions in glycosylated hemoglobin were significantly greater in the liraglutide group than the additional OAD group [estimated mean treatment difference -0.27% (95% confidence interval (CI) -0.44, -0.09; P=0.0026)]; reductions in mean fasting plasma glucose levels were also greater with liraglutide [estimated mean difference -5.47mg/dL (-0.30mmol/L; 95% CI: -10.83, -0.10; P=0.0458)]. Liraglutide was well tolerated and effective as combination therapy with an OAD in Japanese patients with type2 diabetes.

Compliance to treatment and reaching of metabolic goals are better in OAD-treated diabetics than insulin-treated diabetics in the Turkish population

We assessed the success rates of reaching glycated haemoglobin (HbA1c) goals in different treatment groups. Materials and methods: This was a single-centre, retrospective study including 2995 patients. The proportion of patients reaching their HbA1c goals, according to the International Diabetes Federation (IDF), American Association of Clinical Endocrinologists (AACE), and American Diabetes Association (ADA), were determined. Results: There were 4 different treatment groups: 1) diet group (n = 140), 2) oral antidiabetic drug (OAD) group (n = 1238), 3) insulin group (n = 765), and 4) insulin + OAD group (n = 812). According to the IDF and AACE criteria, the proportion of patients reaching HbA1c levels of ≤6.5% was 92% in group 1, and 1 year later it was 100%. In the OAD group the proportions were 61% and 69%, respectively. In the insulin group, the rate was 15% and 1 year later 33% of patients had reached their goals. In the insulin + OAD group, the rates were 10% and 21%, respectively (P < 0.05 for all). According to the ADA criteria, the rate of patients reaching HbA1c levels of =

Insulin glargine plus oral antidiabetic agents in comparison with biphasic insulin in type 2 diabetes: a UK cost comparison

LAPTOP (Lantus + Amaryl + metformin vs. premixed* insulin in Patients with Type-2 diabetes mellitus after failing Oral treatment Pathways) was a multinational study which compared the addition of once daily insulin glargine (IG, Lantus) with the oral antidiabetic drugs (OADs) glimepiride and metformin with twice daily 30% regular/70% human neutral protamine hagedorn (NPH) insulin (Actraphane 30) and no OADs in 371 type 2 diabetes patients over a 24-week period. IG plus OADs was seen to be significantly more effective in lowering glycated haemoglobin A1C (HbA1C) (-1.64% vs. - 1.31%). We undertook a cost minimisation analysis using data from the LAPTOP study to determine the relative costs of the two treatment regimens. Overall, the cost per patient for 24 weeks for the IG plus OADs group was £207.61 compared with £313.49 for biphasic insulin aspart (BIA), a difference of 34%. During the 24-week period of the study the cost of a 1% reduction in HbA1C was £126.59 for IG plus OADs and £239.31 for BIA only. A 1 mmol/L reduction in fasting blood glucose cost £97 with IG plus OADs and £142.50 with BIA. The cost of achieving an equivalent reduction in HbA1C was 34% less with IG plus OADs than twice daily BIA with no OADs.