Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years.

Michael Leutner,Stefan Thurner,Michaela Kaleta,Alexandra Kautzky-Willer,Luise Bellach,Peter Klimek,Alexander Kautzky

doi:10.3390/jpm11100984

Abstract

Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.

Highlights

In the general population, the number of patients with pneumonia is on the rise [1], and healthcare costs are increasing dramatically
We observe that the therapy groups receiving insulin monotherapy, insulin therapy combined with statins, biguanides combined with insulin and statins or therapy with DPP-IV inhibitors combined with insulin and statins show higher relative numbers of patients with the outcome of pneumonia during the observational period when compared to other antidiabetic drug therapies
Patients treated with insulin monotherapy, and in combination with statins, metformin or DPP-IV inhibitors, had an increased risk of diagnosis of pneumonia when compared to individuals without antidiabetic drug therapy

Summary

Introduction

The number of patients with pneumonia is on the rise [1], and healthcare costs are increasing dramatically. Diabetes mellitus is a metabolic disease leading to an increased risk of infections due to the interplay between vascular complications and reduced defense capacities of the immune system [2,3]. Patients with type 2 diabetes are at an increased risk of several complications [4], including infectious diseases such as pneumonia [5,6]. Serious respiratory infections are especially relevant in diabetic patients, since diabetes mellitus can lead to poorer outcomes in lung diseases via multiple pathophysiological mechanisms such as autonomous neuropathy or phrenic nerve neuropathy [12], as well as impairment of the immune system [3]. With further complicating elements like seasonal flu and pneumonia, it is pivotal to search for readily available and cost-effective treatment options to reduce the risk of pneumonia in diabetics

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Conclusion