Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes

Pilla, Scott J.; Dotimas, James; Maruthur, Nisa M.; Clark, Jeanne M.; Yeh, Hsin Chieh

doi:10.1016/j.diabres.2018.02.032

Cited by 8 publications

(11 citation statements)

References 25 publications

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“…[7] This finding is also in agreement with prior studies that found a high proportion of metformin continuation and reported metformin to be the most commonly used therapy in combination with insulin. [12, 13] There is a wealth of evidence to support the benefits of continuing metformin in this setting, including its association with better glycemic control, lower weight gain and lower insulin doses. [8, 14, 15]…”

Section: Discussionmentioning

confidence: 99%

“…The high continuation rates of diabetes medications other than metformin after the transition to insulin were consistent with the previous study on this topic. [12] High rates of continuation were particularly surprising for insulin secretagogues. Use of sulfonylureas or thiazolidinediones in combination with insulin may cause more hypoglycemic episodes and greater weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study examined patterns of diabetes medication use during the insulin transition among participants in a large clinical trial. [12] This study found that within the first year of insulin initiation, metformin was continued among most patients (80.3%), and the majority of patients continued taking -combinations of two or more diabetes medications along with insulin. [13] This study was limited in that medication use was only assessed at yearly intervals, creating a question about how and when such medication changes are occurring.…”

Section: Introductionmentioning

confidence: 99%

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Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study

Pilla

Alexander

et al. 2019

PLoS ONE

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Background Clinical guidelines recommend that metformin be continued after insulin is initiated among patients with type 2 diabetes, yet little is known regarding how often metformin or other non-insulin diabetes medications are continued in this setting. Methods We conducted a retrospective cohort study to characterize rates and use patterns of six classes of non-insulin diabetes medications: biguanides (metformin), sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide 1 receptor agonists (GLP1 receptor agonists), dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors), and sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), among patients with type 2 diabetes initiating insulin. We used the 2010–2015 MarketScan Commercial Claims and Encounters data examining 72,971 patients with type 2 diabetes aged 18–65 years old who initiated insulin and had filled a prescription for a non-insulin diabetes medication in the 90 days prior to insulin initiation. Our primary outcome was the proportion of patients refilling the various non-insulin diabetes medications during the first 90 days after insulin initiation. We also used time-to-event analysis to characterize the time to discontinuation of specific medication classes. Results Metformin was the most common non-insulin medication used prior to insulin initiation (N = 53,017, 72.7%), followed by sulfonylureas (N = 25,439, 34.9%) and DPP4 inhibitors (N = 8,540, 11.7%). More than four out of five patients (N = 65,902, 84.7%) refilled prescriptions for any non-insulin diabetes medications within 90 days after insulin initiation. Within that period, metformin remained the most common medication with the highest continuation rate of 84.6%, followed by SGLT2 inhibitors (81.9%) and TZDs (79.3%). Sulfonylureas were the least likely medications to be continued (73.6% continuation) though they remained the second most common medication class used after insulin initiation. The median time to discontinuation varied by therapeutic class from the longest time to discontinuation of 26.4 months among metformin users to the shortest (3.0 months) among SGLT2 inhibitor users. Conclusion While metformin was commonly continued among commercially insured adults starting insulin, rates of continuation of other non-insulin diabetes medications were also high. Further studies are needed to determine the comparative effectiveness and safety of continuing insulin secretagogues and newer diabetes medications after insulin initiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study

Pilla

Alexander

et al. 2019

PLoS ONE

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“…An observational study done in the US reported more than 70% patients taking metformin before insulin therapy and 80.3% patients continued it after insulin initiation. The proportion of metformin use after insulin therapy was also higher (63.8%) in Pilla et al's study (23). Another study with commercial insurance data also reported 72.7% patients taking metformin before insulin initiation and metformin was continued in 84.6% patients after insulin therapy.…”

Section: Secondary Outcomesmentioning

confidence: 73%

Effectiveness and Safety of Basal Insulin Therapy in Type 2 Diabetes Mellitus Patients With or Without Metformin Observed in a National Cohort in China

Zhang¹,

Zhang²,

Luo³

et al. 2021

Preprint

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Background. Though many randomized control trials had examined the effectiveness and safety of taking insulin therapy with or without metformin, there are limited real-world data, especially among Chinese type 2 diabetes patients initiating basal insulin (BI) with uncontrolled hyperglycemia by oral agents. This study was designed to assess the effectiveness and safety of BI therapy combined with or without metformin in a real-world national cohort study. Methods. Patients with type 2 diabetes mellitus who initiated BI treatment due to uncontrolled hyperglycemia (HbA1c ≥ 7%) by oral antidiabetic drugs (OADs) were recruited in Chinese real-world settings between 2011 and 2013. A total of 12,358 patients initiated BI without bolus insulin and completed a 6-month follow-up were selected as the study population and divided into BI with metformin or BI without metformin group based on whether metformin was simultaneously prescribed or not at baseline. Propensity score adjustment was used to balance baseline covariates between two groups. A sub-analysis was also conducted among 8,086 patients who kept baseline treatment regimen during the follow-up. Outcomes were HbA1c, hypoglycemia, weight gain and insulin dose in two groups. Results. 53.6% (6,621 out of 12,358) patients initiated BI therapy concomitant with metformin. After propensity score adjustment, multivariate regression analysis controlled with number of OADs, total insulin dose, physical activity and diet consumption showed that BI with metformin group had a slightly higher control rate of HbA1c < 7.0% (39.9% vs. 36.4%, P = 0.0011) at 6-month follow-up, and lower dose increment from baseline to 6-month (0.0064 vs. 0.0068 U/day/kg, P = 0.0035). The sub-analysis with patients remained at same BI therapy further showed that BI with metformin group had higher HbA1c control rate (47.9% vs. 41.9%, P = 0.0001), less weight gain (-0.12 vs 0.15 kg P = 0.0013), and lower dose increment during 6-month follow-up (0.0033 vs. 0.0037 U/day/kg, P = 0.0073) when compared with BI without metformin group. Conclusion. In alliance with current guidelines, the real-world findings also support the insulin initiation together with metformin. Continuous patients’ education and clinicians training are needed to improve the use of metformin when initiating BI treatment.

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“…Another potential explanation for this observation is common underdosing of insulin due to fear of causing hypoglycaemia 20 . Furthermore, initiation of insulin treatment is sometimes accompanied by the withdrawal of other glucose‐lowering drugs, which may compromise optimal glycaemic control 21,22 …”

Section: Discussionmentioning

confidence: 99%

What are the factors associated with long‐term glycaemic control in patients with type 2 diabetes and elevated glycated haemoglobin (≥7.0%) at initiation of second‐line therapy? Results from the DISCOVER study

Bonnet

Chen

Cooper

et al. 2021

Diabetes Obesity Metabolism

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Aims Glycaemic control is a cornerstone of type 2 diabetes (T2D) management. We assessed factors associated with good long‐term glycaemic control in patients with glycated haemoglobin (HbA1c) ≥7.0% at initiation of second‐line glucose‐lowering therapy, using data from DISCOVER, a global, prospective, 3‐year observational study of patients with T2D. Materials and Methods This analysis included patients with HbA1c ≥7.0% at baseline (initiation of second‐line therapy). Multivariable regression models assessed factors associated with having HbA1c <7.0% at 3 years in two distinct groups: patients with (a) HbA1c ≥7.0% and <9.0%, and (b) HbA1c ≥9.0% at baseline. Results In total, 7575 patients with baseline HbA1c ≥7.0% were included (2233 with baseline HbA1c ≥9.0%). At 6 months, 43.7% and 24.2% of patients had an HbA1c level <7.0% in groups a and b, respectively; the corresponding proportions at 3 years were 45.8% and 29.3%. Having HbA1c <7.0% at 6 months (vs. ≥7.0%) was the strongest predictor of having HbA1c <7.0% at 3 years in both group a and group b [odds ratio (95% confidence interval): 2.01 (1.77‐2.27) and 2.68 (2.10‐3.41), respectively]. Longer T2D duration was associated with a decreased likelihood of having HbA1c <7.0% at 3 years. Conclusions In patients with poor glycaemic control at initiation of second‐line therapy, early attainment of HbA1c <7.0% appears predictive of long‐term glycaemic control, suggesting that timely modification of treatment strategies in patients with elevated HbA1c after 6 months is important to minimize therapeutic inertia.

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Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes

Abstract: The vast majority of patients with type 2 diabetes continue metformin after insulin initiation, consistent with guidelines. Other antihyperglycemics are frequently continued along with insulin, and further research is needed to determine which, if any, patients may benefit from this.

Cited by 8 publications

References 25 publications

Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study

Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study

Effectiveness and Safety of Basal Insulin Therapy in Type 2 Diabetes Mellitus Patients With or Without Metformin Observed in a National Cohort in China

What are the factors associated with long‐term glycaemic control in patients with type 2 diabetes and elevated glycated haemoglobin (≥7.0%) at initiation of second‐line therapy? Results from the DISCOVER study

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