Page 780 - Basic _ Clinical Pharmacology ( PDFDrive )

766 SECTION VII Endocrine Drugs

TABLE 41–8 Examples of intensive insulin regimens using rapid-acting insulin analogs
(insulin lispro, aspart, or glulisine) and NPH, or insulin detemir, glargine,
or degludec in a 70-kg man with type 1 diabetes. 1–3

Prebreakfast Prelunch Predinner Bedtime
Rapid-acting insulin 5 U 4 U 6 U —
analog
NPH insulin 3 U 3 U 2 U 8–9 U
or
Rapid-acting insulin 5 U 4 U 6 U —
analog
Insulin glargine or — — — 15–16 U
degludec
Insulin detemir 6–7 U — — 8–9 U
1
Assumes that patient is consuming approximately 75 g carbohydrate at breakfast, 60 g at lunch, and 90 g at dinner.
2 The dose of rapid-acting insulin analogs can be raised by 1 or 2 U if extra carbohydrate (15–30 g) is ingested or if premeal blood glucose
is >170 mg/dL. The rapid-acting insulin analogs can be mixed in the same syringe with NPH insulin.
3 Insulin glargine or insulin detemir must be given as a separate injection.

reduced insulin requirement include newly diagnosed persons and intensive lifestyle interventions (diet and exercise), diabetes self-
those with ongoing endogenous insulin production, long-standing management education, and metformin. If clinical failure occurs
diabetes with insulin sensitivity, significant renal insufficiency, or with metformin monotherapy, a second agent is added. Options
other endocrine deficiencies. Increased insulin requirements typi- include sulfonylureas, repaglinide or nateglinide, pioglitazone,
cally occur with obesity, during adolescence, and during the latter GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors,
trimesters of pregnancy. Table 41–8 illustrates regimens of rapidly and insulin. In the choice of the second agent, consideration
acting insulin analogs and basal analogs that might be appropriate should be given to efficacy of the agent, hypoglycemic risk, effect
for a 70-kg person with type 1 diabetes. If the patient is on an on weight, adverse effects, and cost. In patients who experience
insulin pump, he or she may require about a basal infusion rate of
0.6 units per hour throughout the 24 hours with the exception of
4:00 am to 8:00 am, when 0.7 units per hour might be appropriate
(dawn phenomenon). The ratios might be one unit for 12 grams Weight loss + exercise + metformin
carbohydrate plus one unit for 50 mg/dL (2.8 mmol/L) of blood
glucose above a target value of 120 mg/dL (6.7 mmol/L). *

B. Type 2 Diabetes Metformin + another agent
Normalization of glucose levels can occur with weight loss and *
improved insulin sensitivity in the obese patient with type 2 diabetes.
A combination of caloric restriction and increased exercise is neces- Metformin + two other agents
sary if a weight reduction program is to be successful. Understand-
ing the long-term consequences of poorly controlled diabetes may *
motivate some patients to lose weight. For selected patients, medical Metformin + more complex insulin
or surgical options should be considered. Orlistat, phentermine/ regimen ± other non-insulin agent
topiramate, lorcaserin, naltrexone plus extended release bupropion,
and high-dose liraglutide are approved weight loss medications
for use in combination with diet and exercise. Bariatric surgery * Step taken if needed to reach individualized HbA
(Roux-en-Y, gastric banding, gastric sleeve, biliopancreatic diver- target after ~ 3 months. 1c
sion/duodenal switch) typically result in significant weight loss and
can result in remission of the diabetes. FIGURE 41–6 Suggested algorithm for the treatment of type
Nonobese patients with type 2 diabetes frequently have 2 diabetes. The seven main classes of agents are metformin, sul-
increased visceral adiposity—the so-called metabolically obese fonylureas (includes nateglinide, repaglinide), pioglitazone, GLP-1
receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors, insulins.
normal weight patient. There is less emphasis on weight loss in (α-Glucosidase inhibitors, colesevelam, pramlintide, and bromocrip-
such patients, but exercise is important. tine not included because of limited efficacy and significant adverse
Multiple medications may be required to achieve glycemic con- reactions). (Data from the consensus panel of the American Diabetes Association/
trol (Figure 41–6) in patients with type 2 diabetes. Unless there European Association for the Study of Diabetes, as described in Inzucchi SE et al:
is a contraindication, medical therapy should be initiated with Diabetes Care 2012;35:1364.)