Treatment outcomes with the use of a stepwise insulin combinations algorithm among type 2 diabetic patients

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Introduction: In the management of type 2 diabetes, insulin is often started late, when there is failure to achieve good control on maximum oral agents. Clinical inertia to insulin initiation and intensification is widely prevalent in our local setting resulting in poor control of diabetes. This study looked into a stepwise insulin combinations treatment algorithm used in an Endocrinology referral clinic at the University of Santo Tomas Hospital (USTH). It aimed to demonstrate the clinical course of the patients, determine the degree of HbA1c reduction, and show the associated extent of hypoglycemia and weight gain. Methods: This is a retrospective chart review of 104 patients that used the following stepwise treatment: Oral regimen; Regimen A: basal+oral; Regimen B: basal+premeal bolus TID±oral; Regimen C: premixed aspart 70/30 or lispro 75/25 TID or BID with prelunch bolus, ± oral; Regimen D: premixed 70/30 BID+premeal bolus TID ± oral; Regimen E: premixed 70/30 BID+premeal bolus TID+basal ±oral. All received automatic snacking two hours after main meals to prevent hypoglycemia. Patients were educated on proper diet and exercise. Data was analyzed using paired t-test, frequencies and percentages. Results: Most ended on the intensive insulin regimens D 57(55%), and E 18 (17%). Significant HbA1c reduction was demonstrated as follows: Regimen A (n=8):1.376±0.919 (p=0.000), Regimen B (n=18):2.320±2.177 (p=0.000), Regimen D (n=57):2.197±2.158 (p=0.000), Regimen E (n=18):2.684±1.689 (p =0.000). Overall mean weight gain was 1.070 ± 11.435 kg (p=0.335). Ten, non-severe hypoglycemia events were reported. Conclusion: The use of this stepwise insulin combinations treatment algorithm exerted significant HbA1c reduction, with minimal events of hypoglycemia, and statistically insignificant weight gain. Hence, this is a feasible tool that may be used as a guide for intensification of insulin treatment.

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... A stepwise approach may be an effective tool for insulin intensification as this could significantly bring down the levels of HbA1c with minimal occurrence of hypoglycemia and insignificant weight gain. [26] This could guide physicians in using a more complex insulin regimen that would cater to the natural course of type 2 diabetes. ...
... The aging process also contributes to peripheral insulin resistance due to a possible post-receptor defect mechanism. [26] One must remember that in prescribing insulin, one size fits all does not apply-dose and frequency may vary patient per patient but guides given above would help a physician in achieving desired targets. ...
... As shown above, there are several barriers to insulin therapy-risk of hypoglycemia, weight gain and inexperience by the physician, all of which may lead to treatment inertia. [26] Among these, the risk of hypoglycemia restricts most physicians in using insulin despite its limitless capacity and effectiveness to reduce and normalize HbA1c. [9] Previous literatures showed that severe hypoglycemia is associated with increased cardiovascular outcome (eg, myocardial infarction, heart failure and stroke) and all-cause mortality. ...
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In 2021, 537 million adults were living with diabetes. Being a progressive disease, there would eventually be failure of oral hypoglycemic agents (OHA) to maintain good glycemic control and a majority will require insulin. However, optimal glycemic control has not been satisfactory in a significant proportion of patients who were on insulin therapy. Patient factors (eg, awareness, compliance, socioeconomic) have been identified but physician-related factors are as important. These include incorrect choice and inappropriate combination of insulin therapy which could be corrected by making the treatment physiologic. The purpose of this article is to improve management decisions in type 2 diabetes by reviewing its pathophysiology and identifying the optimum insulin regimen that could mimic such. Since eventual beta cell failure is central to its pathophysiology, it is but reasonable to replace insulin by mimicking its physiologic secretion. Hence, the term Insulin Replacement Therapy (IRT) should be utilized. This could be provided by the combination of premix insulin (ie, NPH + regular insulin) and rapid-acting insulin which has been reported to provide an initial 17.5% HbA1c reduction and even 18% reduction on 5-year follow-up providing sustainable control. A stepwise approach is an effective tool for insulin intensification. Hypoglycemia in insulin therapy could be prevented with an appropriate dietary regimen through automatic snacking. Keywords: Insulin replacement therapy, type 2 diabetes mellitus, pathophysiology
... Several reasons why clinicians refrain from starting insulin or intensifying insulin treatment include the risk for hypoglycemia, weight gain and patient's anxiety over insulin use. In a study by Lopez et al. [13], a stepwise insulin combinations treatment algorithm was used as a guide for insulin intensification with the aim of HbA1c reduction taking into consideration hypoglycemic events and influence on weight gain. This treatment algorithm which includes oral regimen used singly or in combination (metformin, sulfonylurea, thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor; regimen A (basal insulin + oral regimen); regimen B (basal insulin + pre-meal bolus three times daily ± oral regimen except sulfonylurea); regimen C (premixed aspart 70/30 or premixed lispro 75/25 three times daily before meals, or premixed aspart 70/30 or premixed lispro 75/25 pre-breakfast and pre-dinner, + pre-lunch lispro or aspart bolus, ± oral regimen); regimen D (premixed human insulin 70/30 twice daily + pre-meal bolus of aspart or lispro, ± 92 oral regimen); and regimen E (regimen D + basal insulin) may actually help physicians even non-specialists to adhere to early insulinization. ...
Background: This study aimed to determine long-term effect of intensive insulin therapy on prevention, progression, and development of chronic diabetes complications, both micro and macrovascular events. This study also aimed to evaluate long-term sustainability of glycemic control of patients on intensive insulin treatment. Methods: A retrospective review of adult type 2 diabetes mellitus (T2DM) patients on intensive insulin therapy for ≥7 years. Demographic data, co-morbidities, body mass index (BMI), hemoglobin A1c (HbA1c), hospitalization were collated. Majority received intensive insulin therapy with combination of premixed 70/30 given two times a day and fast short acting analogue given premeal three times a day, with the addition of glargine or degludec once a day in some. Results: Among 76 patients, 62% were males and 38% were females. Mean age at diagnosis and last visit were 53 and 65 years, respectively. At time of diagnosis, patient had the following co-morbidities: hypertension (32%), dyslipidemia (13%), non-dialyzable chronic kidney disease (CKD) (4%), thyroid disease (1%), pulmonary tuberculosis (1%). In terms of long-term complications, event rates during follow up period are as follows: 0.001 per person-year for acute coronary event; 0.002 per person-year for CKD needing dialysis, 0.009 per person-year for cerebrovascular accident. There were no blindness and amputation observed. There is a statistical difference between HbA1c levels at time of diagnosis (8.53 ± 1.86) and last follow up (7.83 ± 1.71) (P = 0.00). After a median follow up of 12 years (7–22 years), glycemic control was sustained with an HbA1c of ≤7% and ≤8% in 32% and 45% of patients, respectively. Conclusion: With intensive insulin therapy, micro and macrovascular complications can be prevented significantly. Long-term sustainability of glycemic control was also achieved.
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