Insulin therapy combination

Thiazolidinediones may produce fluid retention and edema however, the mechanism by which this occurs is not completely understood. It is known that blood volume increases approximately 10% with these agents, resulting in approximately 6% of patients developing edema. Thus, these drugs are contraindicated in situations in which an increased fluid volume is detrimental, such as heart failure. Fluid retention appears to be dose-related and increases when combined with insulin therapy. 

Several years have passed since you have been following MF s therapy. His weight is down to 230 lb (104.6 kg), and he tries to maintain his diet and exercise. His recent HbAlc levels have increased up to 8.4% from 7.2% despite combination therapy with sulfonylureas and metformin. The physician believes that it is time to start insulin therapy for MF and asks you to initiate therapy and follow his regimen. 

Symptomatic patients may initially require insulin or combination oral therapy to reduce glucose toxicity (which may reduce /1-cell insulin secretion and worsen insulin resistance). 

Combination insulin therapy Concurrent administration of insulin and an oral... 

Combination insulin therapy-The recommended dose is 8 mg once daily with the first main meal with low-dose insulin. 

Should secondary failure occur with metformin or sulfonylurea monotherapy, combined therapy with metformin and sulfonylurea may result in a response. Should secondary failure occur with combined therapy, it may be necessary to consider therapeutic alternatives, including initiation of insulin therapy. 

When acarbose is combined with insulin, the greatest effects are seen with regimens that involve only once- or twice-daily administration. The alpha-glucosidase inhibitors seem to be less effective when they are combined with intensive insulin therapy (35). In combination with insulin or oral hypoglycemic drugs the frequency of hypoglycemic episodes can increase sucrose or higher carbohydrates are reported to be less effective, which can be understood from the mechanism of action. 

Furlong NJ, Hulme SA, O Brien SV, Hardy KJ. Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy. Diabetes Care 2002 25(10) 1685-90. 

Scheen AJ. Combined thiazolidinedione-insulin therapy should we be concerned about safety Drug Sat 2004 27 841-56. 

Although most patients with type 2 diabetes are expected to ultimately require insulin to control their disease, combination with oral medications may obviate the need for nonphysiologically large doses of insulin. This combination may improve glycemic control as well as minimize many of the undesirable side effects of insulin therapy, including weight gain and hyperinsulinemia (126). 

Combining metformin with insulin therapy has been shown to result in less weight gain and better glycemic control with lower insulin requirements Continue combination oral agent therapy + sulfonylurea... 

Jaber LA, Nowak SN, Slaughter RR Insulin-metformin combination therapy in obese patients with type 2 diabetes. J Clin Pharmacol 25 89-94, 2002. 

Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH. Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy. Clin Ther 2004 26(12) 2034-2044. 

Kilo C, Mezitis N, Jain R, Mersey J, McGill J, Raskin P. Starting patients with type 2 diabetes on insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin. J Diabetes Comphcat 2003 17(6) 307-313. 

More recently, metformin has been used successfully in different forms of anti-diabetic triple therapy [30-34], which are becoming more and more popular to avoid insulin therapy. In these smdies metformin was either combined with sulfonylureas and thiazolidendiones, or with sulfonylureas and Exenatide and in the end also with thiazolidendiones and insulin as proposed as the final step in the recently published ADA-EASD algorithm [22]. In a recent review [22] the triple therapy (metformin plus sulfonylurea plus thiazohdendione) was seen relatively critical. It should be considered only when patients are already close to target and when circumstances make it difficult to use insulin. Furthermore, the combination of three oral agents is more expensive than using insulin plus metformin, and no benefit has been shown. 

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