Non-insulin Antidiabetic Agents Research Articles

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Acute Diabetes Complications After Transition to a Value-Based Medication Benefit

The association of value-based medication benefits with diabetes health outcomes is uncertain. To assess the association of a preventive drug list (PDL) value-based medication benefit with acute, preventable diabetes complications. This cohort study used a controlled interrupted time series design and analyzed data from a large, national, commercial health plan from January 1, 2004, through June 30, 2017, for patients with diabetes aged 12 to 64 years enrolled through employers that adopted PDLs (intervention group) and matched and weighted members with diabetes whose employers did not adopt PDLs (control group). All participants were continuously enrolled and analyzed for 1 year before and after the index date. Subgroup analysis assessed patients with diabetes living in lower-income and higher-income neighborhoods. Data analysis was performed between August 19, 2020, and December 1, 2023. At the index date, intervention group members experienced employer-mandated enrollment in a PDL benefit that was added to their follow-up year health plan. This benefit reduced out-of-pocket costs for common cardiometabolic drugs, including noninsulin antidiabetic agents and insulin. Matched control group members continued to have cardiometabolic medications subject to deductibles or co-payments at follow-up. The primary outcome was acute, preventable diabetes complications (eg, bacterial infections, neurovascular events, acute coronary disease, and diabetic ketoacidosis) measured as complication days per 1000 members per year. Intermediate measures included the proportion of days covered by and higher use (mean of 1 or more 30-day fills per month) of antidiabetic agents. The study 10 588 patients in the intervention group (55.2% male; mean [SD] age, 51.1 [10.1] years) and 690 075 patients in the control group (55.2% male; mean [SD] age, 51.1 [10.1] years) after matching and weighting. From baseline to follow-up, the proportion of days covered by noninsulin antidiabetic agents increased by 4.7% (95% CI, 3.2%-6.2%) in the PDL group and by 7.3% (95% CI, 5.1%-9.5%) among PDL members from lower-income areas compared with controls. Higher use of noninsulin antidiabetic agents increased by 11.3% (95% CI, 8.2%-14.5%) in the PDL group and by 15.2% (95% CI, 10.6%-19.8%) among members of the PDL group from lower-income areas compared with controls. The PDL group experienced an 8.4% relative reduction in complication days (95% CI, -13.9% to -2.8%; absolute reduction, -20.2 [95% CI, -34.3 to -6.2] per 1000 members per year) compared with controls from baseline to follow-up, while PDL members residing in lower-income areas had a 10.2% relative reduction (95% CI, -17.4% to -3.0%; absolute, -26.1 [95% CI, -45.8 to -6.5] per 1000 members per year). In this cohort study, acute, preventable diabetes complication days decreased by 8.4% in the overall PDL group and by 10.2% among PDL members from lower-income areas compared with the control group. The results may support a strategy of incentivizing adoption of targeted cost-sharing reductions among commercially insured patients with diabetes and lower income to enhance health outcomes.

Non-Insulin Antidiabetic Agents in the Management of Hyperglycaemia of Non-Critical Hospitalized Patients

Hyperglycaemia affects more than 30% of adults hospitalized for non-critical illness and is associated with an increased risk of adverse clinical outcomes. Insulin therapy is widely used for its safety and efficacy. However, given the growing availability of new drugs and new classes of antidiabetic agents with benefits beyond glycaemic control, challenges arise regarding their use in the hospital setting. This article aims to review and summarize the most recently available evidence and recommendations on the role of non-insulin antidiabetic agents in the management of hyperglycaemia in hospitalized patients. Insulin therapy remains the method of choice. Dipeptidyl peptidase 4 inhibitors can be considered in mild to moderate hyperglycaemia. Glucagon-like peptide 1 receptor agonists have recently shown promising results, with high efficacy in glycaemic control and low risk of hypoglycaemia. There are concerns regarding the increased risk of acidosis with metformin use, especially in cases of acute illness, although there is no evidence to support its suspension in selected patients with relative clinical stability. Sodium-glucose cotransporter-2 inhibitors should be discontinued in clinical situations that may predispose to ketoacidosis, including episodes of acute illness. The hospital use of sulfonylureas and thiazolidinediones is not advised.

Light and Shadow of Na-Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Points for Improvement Based on Our Clinical Experience.

We analyzed the effect of Na-glucose cotransporter 2 inhibitors (SGLT2-I) in diabetic patients visiting our hospital. The study included 236 patients treated with SGLT2-I alone or with codiabetic drugs for at least two years. We analyzed overtime changes in glycosylated hemoglobin A1c (HbA1c) in the patients by repeated analyses of variance (ANOVA) and evaluated the therapeutic effect. HbA1c levels decreased significantly in the first six months after treatment. Afterward, they leveled off and increased slightly over the next two years. Six months after treatment, the mean (SD) of HbA1c was 8.19 (1.46) %; the mean difference dropped by 0.91%, and HbA1c in mild DM2 did not drop by below 8.0%. Overall, there was only a slight improvement. We performed multivariate logistic regression analysis using a model with or without improvement as the objective variable and several explanatory variables. Na and Hct were significant factors. They increased considerably over six months and then leveled off. eGFR significantly reduced in the hyperfiltration group six months after treatment. The annual decline rate in eGFR was also faster, even in the nonhyperfiltration group than in the healthy subjects, which may be a characteristic of renal clearance in SGLT2-I treatment. In conclusion, SGLT2-I is an excellent antidiabetic, nephroprotective agent to eliminate hyperfiltration, but unfortunately, SGLT2-I alone does not have enough power to reduce blood glucose levels. SGLT2-I, with insulin or insulin secretagogues, enhances insulin resistance, induces hyperinsulinemia, and exacerbates type 2 DM. In contrast, SGLT2-I, with noninsulin antidiabetic agents and a low-carbohydrate diet, may bring better results.

Anti-Diabetic Agents in Covid-19, Their Possible Role Beyond Diabetes

Recent reports from various observational investigations revealed and published the outcomes of Non-insulin Anti-diabetic agents. Patients additionally with Type-II Diabetes Mellitus and coronavirus disease, caused by severe acute respiratory syndrome [SARS] has become widespread disease in the world since last 3 years. Age, sex, ethnicity, obesity and co-morbidities all apparently enhance the risk of worst consequences. Glucose lowering drugs and anti-viral drug treatment could limit the risk but impose restrictions on their usage which needs to be carefully assessed. This severe acute respiratory syndrome [coronavirus] might be a potentially triggering and worsen the aspect for the diabetic patients that can bring about severe metabolic complications effecting β-cell function leading to hyperglycaemia and diabetic ketoacidosis.

The use of glucose-lowering medications for the treatment of type 2 diabetes mellitus during pregnancy in the United States.

IntroductionSome guidelines allow for the use of either insulin or noninsulin antidiabetic agents for gestational diabetes, but only insulin is recommended for pregnant women with preexisting type 2 diabetes mellitus (T2DM). We aimed to document treatment patterns in routine care for women with preexisting T2DM.MethodsWe identified pregnancy cohorts within 2 US claims databases for publicly and privately insured individuals: the Medicaid Analytical eXtract (2000–2014) and OptumClinformatics (2004–2014). T2DM was classified with a validated algorithm using ICD‐9‐CM and CPT codes. We assessed medication usage over the years of the study, and changes in medication use before and after the beginning of pregnancy, using prescription fills as a proxy for the use of insulin, metformin, sulphonylureas and other noninsulin antidiabetic agents before pregnancy and during each trimester.ResultsAmong 12,631 women with T2DM, insulin use in pregnancy was stable over the study years (55%–60% in the 2nd trimester), but 2nd trimester use of metformin increased from <5% to 20%. Over the study period, 41% of women filled a prescription for metformin before pregnancy, 37% in the 1st trimester and 17% in the 2nd trimester. By the 2nd trimester, few women used sulphonylureas (11%) or other noninsulin antidiabetic agents (1%). Of the women on metformin only before pregnancy, 36% switched to insulin only by 2nd trimester, 11% added insulin and 16% continued on metformin only. Of the women on metformin and insulin before pregnancy, 61% switched to insulin only by 2nd trimester, 22% continued with metformin and insulin and <5% used only metformin.ConclusionThe use of insulin‐metformin combinations and other noninsulin antidiabetic drugs during pregnancy has increased. Safety studies for these medication regimens are needed.

Retrospective nationwide study on the trends in first-line antidiabetic medication for patients with type 2 diabetes in Japan.

Aims/IntroductionTo investigate the national trend in the prescription of first‐line non‐insulin antidiabetic agents and total medical costs (TMCs) after prescribing the drug in Japanese patients with type 2 diabetes.Materials and MethodsUsing the National Database of Health Insurance Claims and Specific Health Check‐ups of Japan covering almost the entire Japanese population, we calculated the proportion of each antidiabetic drug from 2014 to 2017, and determined the factors associated with drug selection. The TMCs in the first year after starting the drugs were calculated, and factors associated with the costs were also determined.ResultsAmong 1,136,723 new users of antidiabetic agents, dipeptidyl peptidase‐4 inhibitors were the most prescribed (65.1%), followed by biguanides (15.9%) and sodium–glucose cotransporter 2 inhibitors (7.6%). Sodium–glucose cotransporter 2 inhibitor and biguanide use increased during 2014–2017 (2.2%–11.4% and 13.7%–17.2%, respectively), whereas the others decreased. Biguanides were not prescribed at all in 38.2% of non‐Japan Diabetes Society‐certified facilities. The TMCs were the lowest among those who started with biguanides. Fiscal year, age, sex, facility, number of beds and comorbidities were associated with drug choice and TMCs. There were wide regional variations in the drug choice, but not in the TMCs.ConclusionsUnlike in the USA and Europe, dipeptidyl peptidase‐4 inhibitor is the most prescribed first‐line medication for type 2 diabetes patients in Japan, while there is a wide variation in the drug choice by facility‐type and prefecture.

1086-P: A Retrospective Nationwide Surveillance on the First-Line Antidiabetic Medication for the Patients with Type 2 Diabetes in Japan

Background: To investigate the national trend in prescription of first-line non-insulin antidiabetic agents and the annual total medical costs since the first prescription in Japanese patients with type 2 diabetes. Materials and Methods: Using the National Database of Health Insurance Claims and Specific Health Check-ups of Japan (NDB), we calculated the proportion of each antidiabetic drug from fiscal year (FY) 2014 to 2017 and determined factors associated with drug selection in multivariable logistic regression analyses. The total medical costs (TMCs) in the first year after starting the drugs were calculated and factors associated with the costs were also determined. Results: Among 1,136,723 newly-prescribed patients, dipeptidyl peptidase-4 inhibitors (DPP4i) were most prescribed (65.1%) followed by biguanides (15.9%) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) (7.6%). SGLT2i use increased markedly, as was biguanide gradually increased and other drug use decreased during the study period. Biguanides were not prescribed at all in 38.2% of non-certified facilities by the Japan Diabetes Society. TMCs [adjusted mean, 95% CI] were lowest in biguanides [$4638, 4591-4686] followed by thiazolidinediones [$4670, 4546-4794], moderate in SGLT2i [$5383, 5297-5468] and DPP4i [$5583, 5550-5617], highest in glucagon-like peptide 1 receptor agonist [$8596, 7532-9661] after adjusting for covariates including age and comorbidities. FY, age, gender, type of insurance, facility, number of beds, and comorbidities were associated with drug choice and medical costs in the model. There was wide regional variation in initial choice of antidiabetic drugs but not in the TMCs. Conclusions: Unlike in Europe and the US, DPP4i stands as a first-line treatment in Japan. The wide variation in the drug choice by facility and prefecture may suggest the need to create a new strategy such as algorithms that facilitate appropriate drug selection in Japan. Disclosure R. Bouchi: None. T. Sugiyama: None. A. Goto: None. K. Imai: None. N. Ihana-sugiyama: None. M. Ohsugi: Other Relationship; Self; Kyowa Kirin Co., Ltd., Research Support; Self; Abbott Japan Co., Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Novartis Pharma K. K., Novo Nordisk Pharma Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd. T. Yamauchi: Other Relationship; Self; Abbott Japan LLC, Astellas Pharma Inc., AstraZeneca K. K., Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyorin Pharmaceutical Company, Limited, Kyowa Kirin Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Research Support; Self; Aero Switch, Asahi Mutual Life Insurance Company, Bayer Yakuhin, Ltd., Mitsubishi Corporation Life Sciences Limited, NIPRO Medical Corporation, NTT Docomo Inc., Shionogi &amp; Co., Ltd., Tosoh Corporation. T. Kadowaki: Other Relationship; Self; Asahi Mutual Life Insurance Company, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly Japan K. K., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. K. Ueki: Advisory Panel; Self; Abbott Japan Co., Ltd., AstraZeneca K. K., Bayer Yakuhin, Ltd., Novo Nordisk Pharma Ltd., Poxel SA, Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca K. K., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Health and Labour Sciences Research Grants (20FA1016)

De-Intensification of Antidiabetic Treatment Using Canagliflozin in Patients with Heart Failure and Type 2 Diabetes: Cana-Switch-HF Study.

Canagliflozin is a sodium-glucose co-transporter 2 inhibitor that reduces glycemia as well as the risk of cardiovascular events. Our main objective was to analyze antidiabetic treatment de-intensification and the glycemic efficacy of replacing antidiabetic agents (excluding metformin) with canagliflozin in patients with heart failure and type 2 diabetes with poor glycemic control. In this observational, retrospective, real-world study, we selected patients treated with metformin in combination with ≥2 non-insulin antidiabetic agents or metformin in combination with basal insulin plus ≥1 non-insulin antidiabetic agent. Non-insulin antidiabetic agents were replaced with canagliflozin. Patients were followed-up on at three, six, and 12 months after the switch and a wide range of clinical variables were recorded. A total of 121 patients were included. From baseline to 12 months, the number of antidiabetic agents (3.1 ± 1.0 vs. 2.1 ± 0.8, p < 0.05), basal insulin dose (20.1 ± 9.8 vs. 10.1 ± 6.5 units, p < 0.01), and percentage of patients who used basal insulin (47.9% vs. 31.3%, p < 0.01) decreased. The proportion of patients who used diuretics also declined significantly. In addition, we observed improvement in glycemic control, with an increase in the proportion of patients with glycated hemoglobin <7% from 16.8% at three months to 63.5% at 12 (p < 0.001). Canagliflozin use was also beneficial in terms of body weight, blood pressure, heart failure status, functional class, and cardiovascular-renal risk. There were also reductions in the number of emergency department visits and hospitalizations for heart failure. Moreover, canagliflozin was well-tolerated, with a low rate of drug-related discontinuation. Mounting evidence from randomized controlled trials and real-world studies point to the beneficial profile of sodium-glucose co-transporter type 2 inhibitors such as canagliflozin in patients with heart failure.

Therapeutic inertia in patients with type 2 diabetes treated with non-insulin agents.

To analyze therapeutic inertia in type 2 diabetes (T2D) subjects with suboptimal glycemic control and treated with ≥2 non-insulin antidiabetic agents in a primary care setting. A retrospective study was conducted using electronic medical records from subjects with HbA1c ≥7.0% (≥53 mmol/mol). Therapeutic inertia was defined as the absence of treatment intensification despite suboptimal glycemic control where intensification should have been implemented (HbA1c ≥7.5% [≥58 mmol/mol]). Time to the first intensification with non-insulin antidiabetic agent or insulin and HbA1c values at the time of intensification were evaluated by competing risk analysis. 2652 adults with T2D and HbA1c ≥7.0% (≥53 mmol/mol) were included. During the 4-year follow-up, among 1628 individuals with HbA1c ≥7.5% [≥58 mmol/mol], therapeutic inertia was present in 42.9% of cases. Median time to intensification was 14.5 months (IQR25-75, 4-24 months). In this subgroup, 72.7% of subjects initiated non-insulin agents whereas 27.3% initiated insulin. Mean HbA1c values at initiation of treatment intensification were 8.6% (70 mmol/mol) and 9.2% (77 mmol/mol), respectively. Therapeutic inertia occurred in over 40% of subjects. Treatment intensification took longer and was performed at higher HbA1c than recommended in clinical guidelines. Reducing therapeutic inertia is a priority to achieve therapeutic goals and prevent chronic complications in T2D.

Penetration rates of new pharmaceutical products in Europe: A comparative study of several classes recently launched in type-2 diabetes

BackgroundDifferent countries have their own systems for evaluating new medicines, and they make decisions as to when and how each new medicine is adopted. PurposeTo compare the rate of uptake of new diabetes medicines (dipeptidyl peptidase-4 inhibitors [DPP-4Is], glucagon-like peptide-1 receptor agonists [GLP1-RAs], and sodium-glucose co-transporter-2 inhibitors [SGLT2Is]) in the five most populated European countries. MethodsThe monthly volume of sales of antidiabetic drugs was extracted for each country from the IQVIA™ MIDAS® database for the period 2007 to 2016 and the defined daily doses (DDDs) were calculated. For each new drug, market shares were expressed as a percentage of the total market of non-insulin antidiabetic agents. ResultsSharp differences were observed between the countries. Overall, the highest and fastest rates of uptake were seen for Germany and Spain, compared to lower rates for the UK and Italy. This was especially marked for DPP-4Is, where the market share reached over 30% of non-insulin antidiabetic drugs in Germany and Spain, compared to around 10% in the UK and Italy. In France, there was an initial rapid uptake, which stabilized at around 20% after three years. Rates of uptake were lower for the other drugs, with the GLP1-RAs reaching a market share of 2.5–4.5% in Germany, Spain and France, compared to less than 2.5% in the UK and Italy. The SGLT2Is reached a market share of 5–8% in Spain and Germany, compared to less than 4% in the UK and Italy, and they were not launched at all in France in March 2020. ConclusionThe differences in the uptake of new antidiabetic drugs may reflect different methods for assessing and introducing new medicines, as well as cultural factors. The uptake of the new medicines would appear to be more cautious in the UK and Italy, perhaps due to concerns about cost-effectiveness, whereas in Germany and Spain, and possibly also France, a new medicine's potential benefits may be prioritized.

Antidiabetic medication use in commercially insured children and adolescents in the United States from 2004 to 2019.

To describe the patterns of non-insulin antidiabetic medication use, initiation and adherence in the paediatric population. We conducted a descriptive study of non-insulin antidiabetic medication use in children and adolescents (aged 10-18 years) using real-world data from a nationwide US commercial claims database (January 2004-September 2019). Trends in the prevalence of non-insulin antidiabetic medication use overall and by class were evaluated. Among new users of non-insulin antidiabetic agents, medication adherence was examined using group-based trajectory models. In a cohort of more than 1 million paediatric patients, the prevalence of any non-insulin antidiabetic medication use was 75.7 per 100 000 patients in 2004 and more than doubled to 162.0 per 100 000 in 2019. Biguanides (metformin) was by far the most widely used medication class. The use of newer classes was low (<10 per 100 000), but there was an uptake in the use of glucagon-like peptide-1 receptor agonists after liraglutide received paediatric approval in 2019. Medication adherence was poor during the 18 months after treatment initiation: 79.6% of initiators experienced an early treatment interruption (median time to interruption: 90 days among metformin monotherapy initiators) and 21% of initiators did not return for a prescription refill after the first month. There was a substantial increase in non-insulin antidiabetic medication use among commercially insured paediatric patients from 2004 to 2019. Nearly all patients were treated with metformin, while the use of newer agents remained low. Despite the increase in medication use, short treatment episodes were observed, even among patients with a diagnosis of type 2 diabetes, raising concern over poor adherence.

Changes in List Prices, Net Prices, and Discounts for Branded Drugs in the US, 2007-2018

Most studies that have examined drug prices have focused on list prices, without accounting for manufacturer rebates and other discounts, which have substantially increased in the last decade. To describe changes in list prices, net prices, and discounts for branded pharmaceutical products for which US sales are reported by publicly traded companies, and to determine the extent to which list price increases were offset by increases in discounts. Retrospective descriptive study using 2007-2018 pricing data from the investment firm SSR Health for branded products available before January 2007 with US sales reported by publicly traded companies (n = 602 drugs). Net prices were estimated by compiling company-reported sales for each product and number of units sold in the US. Calendar year. Outcomes included list and net prices and discounts in Medicaid and other payers. List prices represent manufacturers' price to wholesalers or direct purchasers but do not account for discounts. Net prices represent revenue per unit of the product after all manufacturer concessions are accounted for (including rebates, coupon cards, and any other discount). Means of outcomes were calculated each year for the overall sample and 6 therapeutic classes, weighting each product by utilization and adjusting for inflation. From 2007 to 2018, list prices increased by 159% (95% CI, 137%-181%), or 9.1% per year, while net prices increased by 60% (95% CI, 36%-84%), or 4.5% per year, with stable net prices between 2015 and 2018. Discounts increased from 40% to 76% in Medicaid and from 23% to 51% for other payers. Increases in discounts offset 62% of list price increases. There was large variability across classes. Multiple sclerosis treatments (n = 4) had the greatest increases in list (439%) and net (157%) prices. List prices of lipid-lowering agents (n = 11) increased by 278% and net prices by 95%. List prices of tumor necrosis factor inhibitors (n = 3) increased by 166% and net prices by 73%. List prices of insulins (n = 7) increased by 262%, and net prices by 51%. List prices of noninsulin antidiabetic agents (n = 10) increased by 165%, and net prices decreased by 1%. List price increases were lowest (59%) for antineoplastic agents (n = 44), but discounts only offset 41% of list price increases, leading to 35% increase in net prices. In this analysis of branded drugs in the US from 2007 to 2018, mean increases in list and net prices were substantial, although discounts offset an estimated 62% of list price increases with substantial variation across classes.

Insulin glargine compared to neutral protamine Hagedorn (NPH) insulin in patients with type-2 diabetes uncontrolled with oral anti-diabetic agents alone in Hong Kong: a cost-effectiveness analysis

BackgroundInternational guidelines recommend using basal insulin in patients with type-2 diabetes mellitus if glycaemic target cannot be attained on non-insulin anti-diabetic drugs. Available choices of basal insulin include intermediate-acting neutral protamine Hagedorn (NPH) insulin and long-acting insulin analogues like insulin glargine U100. Despite clear advantages of glargine U100, the existing practice in Hong Kong still favours NPH insulin due to lower immediate drug costs.ObjectivesThe objective of this study was to assess the cost-effectiveness of insulin glargine U100 compared to NPH insulin in patients with type-2 diabetes uncontrolled with non-insulin anti-diabetic agents alone in Hong Kong.MethodsThe IQVIA™ Core Diabetes Model (CDM) v9.0 was used to conduct the cost-effectiveness analysis of glargine U100 versus NPH. Baseline characteristics were collected from the Hong Kong Diabetes Registry. Efficacy rates were extracted from a published study comparing glargine U100 and NPH in Asia, utilities from published literature, and costs constructed using the Hong Kong Hospital Authority (HA) Gazette (public healthcare setting). The primary outcome was an incremental cost-effectiveness ratio (ICER).ResultsInsulin glargine U100 resulted in an ICER of HKD 98,663 per Quality Adjusted Life Year (QALY) gained. The incremental gains in QALY and costs were 0.217 years and HKD 21,360 respectively. Results from scenario and probabilistic sensitivity analyses were consistent with that from base case analysis.ConclusionInsulin glargine U100 is a cost-effective treatment for patients with type 2 diabetes compared to NPH insulin in setting in Hong Kong. This was mainly driven by the significantly lower rates of hypoglycaemia of insulin glargine U100 than NPH insulin.

Comparison of non-insulin antidiabetic agents as an add-on drug to insulin therapy in type 2 diabetes: a network meta-analysis

We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and ClinicalTrials.gov through April 2016. Bayesian network meta-analyses were performed with covariate adjustment. The primary outcome was the change in glycated hemoglobin A1c (HbA1c) from baseline. Fifty randomized controlled trials covering 15,494 patients were included. GLP-1RA showed the greatest HbA1c-lowering effect compared to the control (−0.84%; 95% credible interval, −1.00% to −0.69%), followed by TZD (−0.73%; −0.93 to −0.52%), SGLT2i (−0.66%; −0.84% to −0.48%), and DPP4i (−0.54%; −0.68% to −0.39%). SGLT2i showed the greatest fasting plasma glucose reduction. GLP-1RA and SGLT2i showed greater body weight reduction, whereas TZD increased body weight. TZD was ranked the highest in terms of insulin dose reduction. The risk of hypoglycemia was increased with TZD or GLP-1RA. The study provides the best available evidence on the comparative efficacy and safety of non-insulin anti-diabetic agents on top of pre-existing insulin therapy for inadequately controlled T2DM patients.

Nutritional Insulin or Glp-1 Receptor Agonist: Crossroads in the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease due to worsening of pancreatic beta cell function over time ( 1. Fonseca V.A. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009; 32: S151-S156 Crossref PubMed Google Scholar ). Patients with classical T2DM initially respond to noninsulin antidiabetic agents, but insulin therapy becomes essential at some point. Most patients treated with sulfonylurea drugs and metformin need insulin after about 9 years of therapy ( 2. Turner R.C. Cull C.A. Frighi V. Holman R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999; 281: 2005-2012 Crossref PubMed Scopus (2167) Google Scholar ). Once required, insulin is often prescribed as a single daily injection of basal insulin. However, over time, more frequent injections are needed to control postprandial hyperglycemia and achieve a target level of glycated hemoglobin (HbA1c). While insulin is the most effective treatment for hyperglycemia, insulin use is associated with weight gain and increased risk of hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). Moreover, multiple daily insulin injections are prone to errors and may be burdensome for many older patients with T2DM. Therefore, alternatives to daily insulin injections are welcomed by patients as well as their physicians. Adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to a treatment regimen that includes basal insulin and oral antidiabetic agents is an attractive option. Compared to the basal-bolus insulin regimen, it requires a smaller number of injections and is associated with lower risks of weight gain and hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). A GLP-1RA may be added to the basal insulin therapy or vice versa. Randomized clinical trials have shown equivalent glycemic control with basal insulin plus a GLP-1RA and basal insulin plus nutritional insulin ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar , 4. Mathieu C. Rodbard H.W. Cariou B. et al. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab. 2014; 16: 636-644 Crossref PubMed Scopus (144) Google Scholar ). However, there are concerns about using GLP-1RA with insulin due to increased treatment cost.

The evolution of insulin glargine and its continuing contribution to diabetes care.

The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insulin and its chemical synthesis and biosynthesis allowed modification of the insulin molecule itself, resulting in insulin analogs that are designed to mimic normal endogenous insulin secretion during both fasting and prandial conditions. Insulin glargine was the first once-daily, long-acting insulin analog to be introduced into clinical practice more than 10 years ago and is specifically designed to provide basal insulin requirements. It has a prolonged duration of action and no distinct insulin peak, making it suitable for once-daily administration and reducing the risk of nocturnal hypoglycemia that is seen with intermediate-acting insulins. Insulin glargine can be used in combination with prandial insulin preparations and non-insulin anti-diabetic agents according to individual requirements.Electronic supplementary materialThe online version of this article (doi:10.1007/s40265-014-0226-4) contains supplementary material, which is available to authorized users.

The Use of Non-Insulin Anti-Diabetic Agents to Improve Glycemia Without Hypoglycemia in the Hospital Setting: Focus on Incretins

Patients with hyperglycemia in hospital have increased adverse outcomes compared with patients with normoglycemia, and the pathophysiological causes seem relatively well understood. Thus, a rationale for excellent glycemic control exists. Benefits of control with intensive insulin regimes are highly likely based on multiple published studies. However, hypoglycemia frequency increases and adverse outcomes of hypoglycemia accrue. This has resulted in a 'push' for therapeutic nihilism, accepting higher glycemic levels to avoid hypoglycemia. One would ideally prefer to optimize glycemia, treating hyperglycemia while minimizing or avoiding hypoglycemia. Thus, one would welcome therapies and processes of care to optimize this benefit/ risk ratio. We review the logic and early studies that suggest that incretin therapy use in-hospital can achieve this ideal. We strongly urge randomized prospective controlled studies to test our proposal and we offer a process of care to facilitate this research and their use in our hospitalized patients.

Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index

Objective To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens. Data sources We searched databases for primary studies published in English. The main search concepts were type 2 diabetes, insulin treatment, premixed insulin, premixed insulin analogs, basal inuslin, basal inuslin analogs, bolus insulin, bolus insulin analogs, safety and efficacy. Study selection Studies were eligible for inclusion if they met all of the following criteria: (1) type 2 diabetic patients aged &gt;18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated. Results When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 94.44%. When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 45.5%, the proportion of GSCIΔA1c ratio more than 1 was 38.9%. When premixed insulin therapy compared with oral hypoglycemic agents, the proportion of GSCI%A1c ratio less than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 50%. When premixed insulin therapy compared with basal-bolus insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 37.5%, the proportion of GSCIΔA1c ratio more than 1 was 50%. Conclusion According to the GSCI ratio, long-acting basal insulin therapy tended to be superior to NPH therapy, oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy, noninsulin antidiabetic agents and premixed insulin therapy was comparable, and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes.

The Use of Metformin and Colorectal Cancer Incidence in Patients with Type II Diabetes Mellitus

Experimental studies have suggested that metformin may decrease the incidence of colorectal cancer in patients with type II diabetes. However, previous observational studies have reported contradictory results, which are likely due to important methodologic limitations. Thus, the objective of this study was to assess whether the use of metformin is associated with the incidence of colorectal cancer in patients with type II diabetes. A cohort study of patients newly treated with non-insulin antidiabetic agents was assembled using the United Kingdom Clinical Practice Research Datalink. A nested case-control analysis was conducted, where all incident cases of colorectal cancer occurring during follow-up were identified and randomly matched with up to 10 controls. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of colorectal cancer associated with ever use, and cumulative duration of use of metformin. All models accounted for latency and were adjusted for relevant potential confounding factors. Overall, ever use of metformin was not associated with the incidence of colorectal cancer [RR: 0.93; 95% confidence interval (CI), 0.73-1.18]. Similarly, no dose-response relationship was observed in terms of cumulative duration of use. The use of metformin was not associated with the incidence of colorectal cancer in patients with type II diabetes. The results of this study do not support the launch of metformin randomized controlled trials for the chemoprevention of colorectal cancer.