Insulin therapy adjustment

Concomitant metformin IR or ER and insulin therapy in ac/w/fs.Continue the current insulin dose upon initiation of metformin IR or ER therapy. Initiate metformin IR or ER therapy at 500 mg once/day in patients on insulin therapy. For patients not responding adequately, increase the dose of metformin IR or ER by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2,500 mg for metformin IR and 2,000 mg for metformin ER (2,500 mg with Fortamef). It is recommended that the insulin dose be decreased 10% to 25% when FPG concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and metformin IR or ER. Individualize further adjustment based on glucose-lowering response. 

Insulin promotes the sequestration of fat, and weight gain is a common side effect. This is a concern particularly in type 2 diabetes in which obesity is common. In the UKPDS, obese patients on insulin therapy gained an average of 4 kg more than those treated by diet adjustment only. 

Insulin therapy is adjusted based on hourly measurements of blood glucose and - if possible -blood ketones, the overall aim being a gradual decline in both. The initial decline is to a large extent due to rehydration and expansion of the extracellular volume. Repeated analysis of arterial blood gases may be indicated but only in those patients with very low pH values and/or poor chn-ical condition. Measurements of ketone levels in urine is in general unreliable in this phase these methods measure acetoacetate, which is quantitatively of minor importance compared with... 

Somatomedins are insulin-like polypeptide hormones that should be used with caution in diabetic patients since adjustment of antidiabetic therapy may be required. Before initiating therapy, a baseline ECG is recommended and, if abnormalities are identified, regular ECG monitoring during treatment is required. Somatomedins may cause tachycardia, cardiomegaly, ventricular hypertrophy and changes in blood glucose levels as side-effects. 

Mudaliar S et al New oral therapies for type 2 diabetes mellitus The glitazones or insulin sensitizers. Annu Rev Med 2001 52 239. [PMID 11160777] Nathan DM et al Management of hyperglycemia in type 2 diabetes mellitus A consensus algorithm for the initiation and adjustment of therapy. Diabetes... 

Lipodystrophy, a syndrome characterized by fat redistribution, hyperglycemia/insulin resistance, and dyslipidemia, can be associated with long-term HIV infection or with highly active antiretroviral therapy (HAART). In 1035 patients, those who took stavudine were 1.35 times more likely to report lipodystrophy (1076). However, the study was retrospective, and other factors unrelated to specific drug therapy may have had a greater effect on the adjusted odds ratio. 

It is well known that diabetic patients undergoing coronary interventions have worse chnical and angiographic outcomes in comparison with nondiabetic patients. In the retrospective analysis of the PRESTO (Prevention of Restenosis with Tranilast and its Outcomes) trial the effect of different anti-diabetic treatment was analysed [40] in 1,110 diabetic patients who received non-sensitizer therapy (insulin and/or sulfonylureas) and in 887 patients who were treated with sensitizers (metformin with or without additional therapy). Compared with patients on non-sensitizer therapy, those on sensitizer therapy showed an adjusted OR of 0.72 p = 0.005 for any clinical event. The differences between the non-sensitizer therapy group and the sensitizer group were attributable mainly to decreased rates of death (OR = 0.39 p = 0.007) and myocardial infarction (OR = 0.31 p = 0.002). In this retrospective analysis, use of metformin in diabetics undergoing coronary interventions appeared to decrease adverse clinical events, especially death and myocardial infarction, compared with diabetic patients treated with non-sensitizer therapy. 

The ultimate goal of insulin replacement therapy is a closed-loop controlled system or device in which the insulin release rates are adjusted by the system in response to glucose levels in the blood. Several different approaches for glucose-responsive insulin delivery have been investigated. 

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