Titration is targeted at fasting plasma glucose (FPG). • Released at Lantus. Glargine U/ml. Toujeo. Glargine U/ml. Tresiba. Degludec. Novolog 70/30 . (*Inform patient to hold titration until further evaluation if develops any . Start NPH before bed at 40% of total daily Lantus/Levemir dose* (then titrate per basal . Basal Insulin Therapy and Basal Insulin Titration Algorithms for T2DM: What Is of insulin glargine—following a specific titration algorithm—added to metformin.

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Type 2 diabetes mellitus has become a worldwide major titratino problem, and the number of people affected is steadily increasing. Thus, not all patients suffering from the disease can be treated by specialized diabetes centers or outpatient clinics, but by primary care physicians.

The latter, however, might have time constraints and have to deal with many kinds of diseases or with multimorbid patients, so their focus is not so much on lowering ittration blood glucose values.

Thus, the physicians, as well as the patients themselves, are often reluctant to initiate and adjust insulin therapy, although basal insulin therapy is considered the appropriate strategy after tittation antidiabetic drug failure, according to the latest international guidelines. A substantial number of clinical studies have shown that insulin initiation and optimization can be managed successfully by using titration algorithms—even in cases where patients themselves are the drivers of insulin titration.

Nevertheless, tools and strategies are needed to facilitate this process in the daily life of both primary health care professionals and titrafion with diabetes. There is a worldwide increase in the prevalence and incidence of diabetes, with new figures indicating a rise from million people concerned in to million by Type 2 diabetes patients face a dramatically increased risk of cardiovascular and cerebrovascular morbidity and mortality.

Common Standards of Basal Insulin Titration in T2DM

It can be anticipated that the predicted rise in the prevalence of T2DM 2 and the trend to develop diabetes earlier in life will lead to a further increase latus diabetes complications, including also diabetic visual impairment, renal failure, and amputations.

This review will give an overview on basal insulin therapy for T2DM in daily life, taking into account recommendations by international guidelines, the use of titration algorithms, kantus future perspectives for patients and primary care physicians.

Quite a number of national 4—7 and international 8—10 guidelines on the treatment of T2DM exist. All guidelines give recommendations on glycemic targets for T2DM [hemoglobin A1c HbA1cblood glucose values], on blood glucose self-monitoring by the patients, and on therapeutic options, including specific treatment regimens.

The aforementioned guidelines, however, vary considerably—not only in size and scope, but also with regard to time and mode of insulin initiation and with regard to targets HbA1c. After initial drug monotherapy, i. During self-titration, frequent contact with the physician may be necessary. Remarkably, the position statement points out that practitioners themselves, of course, could also titrate basal insulin but that this would involve more intensive contact with the patient than typically available in routine medical care.

Basal insulin should primarily be titrated against the FBG—generally irrespective of the total dose—although the physician should be aware that prandial insulin might be needed if the daily dose exceeds 0. Given the estimate of an increasing number of people with T2DM on the one hand and the limited availability of health care resources on the other hand, it is easy to conclude that there is an obvious mismatch between supply and demand.

It already is and will continue to be unfeasible to treat all patients with T2DM in specialized diabetes clinics or diabetes outpatient titratlon.

Dosing of insulin glargine in the treatment of type 2 diabetes.

The the majority of patients are and continue to be treated in a primary care setting, i. These primary care providers, however, are often reluctant and apprehensive about using insulin in patients with T2DM. These factors could lead to an undue delay in making the necessary transition from oral agents to insulin. In another investigation 19 on diabetes knowledge carried out among internal medicine residents, family practice residents, surgery residents, and registered nurses, a question survey revealed similar, but insufficient, levels of knowledge in these groups.

Surgery residents had a more pronounced deficit of diabetes knowledge, whereas additional previous diabetes training among nurses was associated with greater diabetes knowledge.

Nevertheless, insulin initiation with basal insulin including insulin analog in patients with T2DM can be managed successfully in both primary and secondary care, as shown in a 3-month longitudinal observational study across centers in France; 22 mean HbA1c and FBG values decreased by 1.


Tittration first basal insulin evaluation or FINE Asia study 16 also demonstrated effective and safe insulin initiation in patients from 11 Asian countries in a real-world setting. A number of reviews and meta-analyses or pooled analyses deal with basal insulin therapy, including insulin initiation and titration algorithms for T2DM.

Largest week HbA1c reductions were observed for patients on 0 or 1 OAD or on metformin monotherapy at baseline; Weight gain was also lantks when basal insulin was added to metformin, as were hypoglycemic events. A later review 25 stresses the urgent need of more simple, clear, consistent, and sustainable treatment regimens and guidelines. The authors also emphasize that enforced intensification of unrealistic complex treatment regimens and glycemic targets may theoretically worsen the psychological wellbeing of some patients.

In addition, numerous studies have lants published on basal insulin therapy in patients with T2DM and on basal insulin regimen in combination with OADs or short-acting insulins with specific titration algorithms.

In the three-year 4-T study, 44 subjects with T2DM and poor glycemic control on metformin and sulfonylurea were randomly assigned to get basal insulin detemir or biphasic insulin aspart or prandial insulin aspart.

Thus, the tihration 4-T trial also supports the initiation of basal insulin. This is supported by the concept that fasting hyperglycemia has a greater impact on HbA1c levels than has lanuts hyperglycemia, which was demonstrated earlier by Monnier and coauthors; 56 the relative contribution of fasting hyperglycemia to HbA1c levels increased gradually as lanrus proceeded, whereas that of postprandial glucose excursions was prevailing in fairly well-controlled patients.

Therefore, this also emphasizes the need to focus on FBG during insulin therapy—especially basal insulin therapy—in T2DM. All trials have consistently shown substantial improvements in glycemic control as indicated by reductions in HbA1c values and FBG together with a low number of hypoglycemic episodes.

The following important aspects however, should be noted when evaluating basal insulin titration algorithms see Appendix 1 for details including studies:. Taking all aspects together, there appears to be an apparent gap between international guideline recommendations, the results of clinical trials, and real-life clinical practice 25 as far as basal insulin initiation and treatment optimization in T2DM—including titration algorithms—is concerned.

One pilot trial investigated the translation of comparative effectiveness into practice by developing and using a decision aid tool, which proved to be acceptable to patients and providers and effective for knowledge translation. Use of the template was associated with improved mean blood glucose levels without increasing hypoglycemia in patients with T2DM.

Another option could consist of automated insulin dose calculators as supportive tools for both patients with T2DM starting basal insulin therapy and the primary care physician who is treating these patients. Such calculators already exist for bolus insulin primarily for insulin pumps or intensive care unitsand several studies gitration such devices or programs have been published. This improvement of diabetes control should be proven in controlled trials.

One major and still unmet need in diabetes therapy is therefore the translation of simple and effective treatment strategies to daily practice and the empowerment of patients who need insulin to self-manage this therapy. The first step to achieve this aim would be to strengthen the self-confidence of patients to master the initiation of insulin treatment, to address their fears, and to provide practical and effective algorithms for initiation and subsequent dose adaptation of insulin administration.

Type 2 diabetes has become a major health burden with further increasing prevalence rates. The majority of patients already is and will be treated by primary care physicians. Numerous clinical trials have shown that basal insulin can be initiated successfully using basal insulin titration algorithms.

Such algorithms can even be handled successfully by the patients themselves, as seen by substantial improvements in metabolic control, i. Practical tools, however, are needed to support patients ittration their physicians and to facilitate everyday life and thereby to prevent undue and harmful delay in initiating necessary insulin treatment.

Dosing of insulin glargine in the treatment of type 2 diabetes.

A successful option totration this context titratoin be a therapeutic strategy that takes into account patient-relevant aspects of care and facilitates the initiation and titrayion adaptation of insulin treatment using an automated basal insulin dose calculator that is simple to use and effective in achieving the agreed therapeutic targets.

The clinical outcome of this approach should be proven in controlled trials. The lantsu of this article and opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication. Most studies used a starting insulin dose titratiin 10 U per day, 12,13,37,40,42,43,46,47,50,52,54 others used slightly higher 51,53 for patients on more than one OAD or lower 45,52 doses for some populations or based their starting insulin dose recommendation on a formula 11,41 or on units per kilogram body weight.


A common theme as part of most of the algorithms is a titration step of 2 U. Sometimes this is the sole titration instruction. In other studies, this is part of a sequence of titration steps with higher or lower dose increase depending on the blood glucose level.

Only one study used bigger steps of 3 U, 48 and another one used smaller steps of 1 to 2 U. The burden of work on health care professionals means they need an algorithm that fits with the frequency at which they can contact the patient, typically weekly in studies.

It is important to note that, as described by Swinnen and coauthors, 73 the biggest predictor of success in basal insulin titration seems to be contact frequency, enforcing the titration. For patients, little and often is both easier and safer: Patient algorithms in almost all studies are labtus per week or every 3 days or every day.

HbA1c values decreased, with a substantial proportion of patients achieving levels below 7. All studies showed quite pronounced improvements in terms of HbA1c between 0. In contrast to the well-described and standardized titration schedules for the up-dosing of insulin to reach target, insulin dose reduction to counterbalance hypoglycemic events is much less standardized.

Sulfonylureas could be continued, if applicable, with the exception of one study. Another study discontinued thiazolidinediones. A higher variation was seen in older subjects and in those with longer duration of insulin therapy, greater consumption of sugars, and greater confidence in their self-care abilities. Lower variations were observed in obese subjects, subjects who were more compliant, and those receiving larger insulin doses. Multivariate analyses demonstrated that treatment duration, sugar consumption, medication compliance, and insulin doses were independently associated with glucose variation.

Fasting variation was more influenced by medication compliance, whereas, before lunch, variation was more strongly influenced by body mass. Bearing in mind these day-to-day variability factors, it seems appropriate not to titrate the insulin dose too often. Based on clinical experience, dose adjustments every three days as used in several studies could be considered as appropriate in this respect. Longer-term trials have shown that the insulin dose over time keeps increasing, e.

Therefore, a close eye should be kept on insulin dose development in the long run, and one should not miss the point to think of additional—prandial—insulin as soon as this is deemed to be appropriate, e. The key clinical studies cited used different kinds of basal insulin titration algorithms, from few to many steps, different step sizes i.

They also varied as to which person was responsible for the titration: It is of great importance, however, that insulin titration is manageable for the patients in their daily life. Thus titration algorithms should be as simple as possible to support both primary care physicians and patients in optimizing basal insulin therapy. Increased standardization of titration schemes would benefit health care professionals and patients alike.

The algorithms should also be in line with national and international diabetes guidelines that, in addition, need to be consistent in their recommendations. Tim Heise has also served on advisory panels for and received speaker honoraria and travel grants from Boehringer Ingelheim and Novo Nordisk. Frank Flacke and Jochen Sieber are employees of sanofi. National Center for Biotechnology InformationU.

J Diabetes Sci Technol. Published online May 1. Sabine ArnoldsM. Author information Copyright and License information Disclaimer.

This article has been cited by other articles in PMC. Abstract Type 2 diabetes mellitus has become a worldwide major health problem, and the number of people affected is steadily increasing. Introduction There is a worldwide increase in the prevalence and incidence of diabetes, with new figures indicating a rise titrayion million people concerned in to million by What Do Diabetes Guidelines Recommend?

Complexity of insulin therapy is considered too difficult to lantuw managed in a busy primary care practice. Uncertainties regarding initial insulin dosing and titration due to vague prescribing information provided by manufacturers, and.

Lack of self-confidence to manage insulin therapy, Multifactorial psychological resistance to insulin therapy, Fear of hypoglycemia, Need for frequent blood glucose monitoring,