It is a "peakless" insulin

Insulin lispro

15 to 30 minutes before each meal

SGLT2 inhibitor—increases urinary excretion of glucose

Metformin

Glyburide

Liraglutide

Linagliptin

Glipizide—repaglinide

Dapagliflozin

lipolysis, proteolysis, and glycogenolysis

enzyme-linked receptors (tyrosine kinase)

Type I – Loss of beta-cell function and Type I DM results from autoimmune-medicated processes. Type II – Lack of sensitivity of target organs to insulin. The pancreas retains some beta-cell function, but insulin secretion is insufficient to maintain glucose homeostasis in the face of increasing peripheral insulin resistance.

type 1 is treated with only exogenous insulin, whereas type 2 is treated with weight reduction, exercise, diet modificaitons, and medicaitons

type 1 is usually during childhood or puberty, whereas type 2 is commonly over age 35

Type 1 are usually undernourished, account for 5-10% of diabetics, and have a moderate genetic predisposition Type 2 are usually obese, account for 90-95% of diabetics, and have a very strong genetic predisposition

Fasting plasma glucose >/= 126 and A1C >/= 6.5%

31 year old female - Educate her that fasting plasma glucose in the management of diabetes is 80 to 130 mg/dL and that for postprandial glucose is less than 180 mg/dL. 22 year old pregnant female - Educate her that glucose goals are more stringent in patients with gestational diabetes (for example, fasting plasma glucose 70-95 mg/dL, or e, AIC less than 6% if this can be obtained without significant hypoglycemia). 79 year old male - Inform him that he is on track and to keep up the good work since glucose goals may be less stringent in elderly patients (for example, AIC less than 8%)

Metabolic Syndrome

Apple-shaped

High triglyceride levels and HDL cholesterol, Atherosclerosis, Hypertension , Elevated glucose levels, Excessive thirst and hunger , Frequent urination , Blurred vision and headaches, Vaginal and skin infections, Slow-healing cuts and sores, Increased risk of stroke and CV disease, Nerve damage in limbs/loss of limbs

Prediabetes because patients with borderline fasting glucose (100-125 mg/dL), postprandial glucose (140-199, AIC 5.7% to 6.4%) are considered to have prediabetes.

Insulin suppresses hepatic glucose output and adipose tissue lipolysis, lowering blood glucose and fatty acid levels. It also increases hepatic lipid synthesis for subsequent storage in adipose tissue and stimulates glucose uptake into fat and muscle.

Is rapidly triggered in response to increased blood glucose levels and lasts about 10 minutes

Is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours

By slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels

Basal insulin suppresses glucose production by the liver (gluconeogenesis) between meals and overnight. Prandial (bolus) insulin covers increases in blood glucose levels following meals

Rapid Acting

Short Acting

Intermediate Acting

Long Acting

Premixed

Bacteria and yeast

Hypoglycemia could occur starting at the onset of drug action, and if 2 different insulins are used hypoglycemia could occur in the window between onsets.

Aspart, Lispro, Glulisine; prandial control

Regular; prandial control

NPH; basal insulin only when dosed at bedtime, or a basal and prandial insulin when dosed in the morning.

Glargine, Detemir, Degludec; for basal control

70/30 NPH/Regular; basal and prandial

Standard Therapy: -Involves twice-daily injections -Fewer episodes of hypoglycemia (seizures, coma) -Increased microvascular complications Intensive Treatment: -Involves three or more injections daily -More likely to acheive mean blood glucose level of 154 mg/dL or less (AIC s 7%) -Frequency of hypoglycemic episodes, coma, and seizures is higher -More significant reduction in microvascular complications (retinopathy, nephropathy, and neuropathy) -Not recommended for patients with long-standing diabetes, significant microvascular complications, advanced age, and with hypoglycemic unawareness

Regular insulin; Monitor for quicker onset of hypoglycemia

-HgA1C and fasting and post-prandial blood sugar -Consider other co-morbities and drugs that influence blood sugar

Normal = below 5.7%, Prediabetes = 5.7-6.4%, Diabetes = 6.5% and above; Check every 3-6 months

Regular insulin, insulin aspart, insulin lispro, NPH, and insulin detemir

Headache, Anxiety, Tachycardia, Confusion, Vertigo, Diaphoresis, Shakiness, Increased appetite, Blurred vision, Weakness/fatigue, Lipodystrophy at injection site,Weight gain

Reduction of hepatic gluconeogenesis. Metformin also slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization (improves insulin sensitivity). The drug does not promote insulin secretion.

Well absorbed after oral administration, is not bound to serum proteins, and is not metabolized. Excretion is primarily via the kidneys as an unchanged drug

Largely gastrointestinal, including diarrhea, nausea, and vomiting. Weight loss may occur because it causes loss of appetite. Metformin is contraindicated renal dysfunction due to the risk of lactic acidosis. It should be discontinued in cases of acute myocardial infarction, exacerbation of heart failure, sepsis, or other disorders that can cause renal failure. Should be used with caution in patients older than 80 years and in those with a history of alcohol It should be temporarily discontinued in patients undergoing procedures requiring IV radiographic contrast. Rarely, potential lactic acidosis has occurred. Long-term use may be associated with vitamin B12 deficiency, and periodic measurement of B12 levels is recommended, especially in patients with anemia peripheral neuropathy

Stimulation of insulin release from the ß cells of the pancreas. Block ATP-sensitive K+ channels on the cells, resulting in depolarization, Ca2+ influx, and exocytosis of insulin. In addition, may reduce hepatic glucose and increase peripheral insulin sensitivity.

Given orally, these drugs bind to serum proteins, are metabolized by the liver, and are excreted in the urine and feces. The duration of action ranges from 12 to 24 hours.

Include hypoglycemia, hyperinsulinemia, and weight gain. They should be used with caution in hepatic or renal insufficiency, since accumulation may cause hypoglycemia. Renal impairment is a particular problem for glyburide, as it may increase the duration of action and increase the risk of hypoglycemia significantly.

Glipizide or glimepiride

Glyburide, glipizide, and glimepiride

Metformin

Lower insulin resistance by acting as agonists for the peroxisome proliferator—activated receptor-y (PPARy), a nuclear hormone receptor. Activation of PPARY regulates the transcription of several insulin responsive genes, resulting in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle. Can be used as monotherapy or in combination with other glucose-lowering agents or insulin. The dose of insulin may have to be lowered when used in combination with these agents.

Rosiglitazone

Are well absorbed after oral administration and are extensively bound to serum albumin. Both drugs undergo extensive metabolism, primarily by CYP2C8. Some metabolites of pioglitazone have activity. Renal elimination of pioglitazone is negligible, with the majority of active drug and metabolites excreted in the bile and eliminated in the feces. Metabolites of rosiglitazone are primarily excreted in the urine. No dosage adjustment is required in renal impairment

Weight gain can occur because they may increase subcutaneous fat and cause fluid retention. [Note: Fluid retention can worsen heart failure. These drugs should be avoided in patients with symptomatic heart failure.] Have been associated with osteopenia and increased fracture risk in women. Liver toxicity has occasionally been reported with these drugs, and baseline and periodic monitoring of liver function is recommended.

Pioglitazone

Rosiglitazone

Acarbose and miglitol

Located in the intestinal brush border, a-glucosidase enzymes break down carbohydrates into glucose and other simple sugars that can be absorbed. Acarbose and miglitol reversibly inhibit a-glucosidase enzymes. When taken at the start of a meal, these drugs delay the digestion of carbohydrates, resulting in lower postprandial glucose levels.

Alpha glucosidase inhibitors

Alpha glucosidase inhibitors

Acarbose is poorly absorbed. It is metabolized primarily by the intestinal bacteria, and some of the metabolites are absorbed and excreted into the urine. Miglitol is very well absorbed but has no systemic effects. It is unchanged by the kidneys.

The most common adverse effects are flatulence, diarrhea, and abdominal cramping. Patients with inflammatory bowel disease, colonic ulceration, or intestinal obstruction should not use these drugs.

These drugs inhibit the enzyme which is responsible for the inactivation of incretin hormones increases release of insulin in response to meals and reduce propriate secretion of glucagon. May be monotherapy or in combination with sulfonylureas, metformin, or insulin.

DPP4 Inhibitors

DPP4 Inhibitors

Well absorbed after oral administration. Food does not affect the extent of absorption. Alogliptin and sitagliptin are mostly excreted unchanged in the urine. Saxagliptin is metabolized via CYP450 34A/5 to an active metabolite. The primary route of elimination for saxagliptin and the metabolite is renal. Linagliptin is primarily eliminated via the enterohepatic system.

Linagliptin

Are well tolerated, with nasopharyngitis and headache as the most common adverse effects. Although infrequent, serious hypersensitivity reactions and pancreatitis have occurred. Agents in this class may also increase the risk of joint pain, which is severe and disabling in some cases.

Saxagliptin

Incretin effect

The gut releases incretin hormones, notably glucagon-like peptide-I (GLP-I) and glucose dependent insulinotropic polypeptide (GIP), in response to a meal

Dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide

Dulaglutide, liraglutide, and semaglutide

Insulin glargine plus lixisenatide and insulin degludec plus liraglutide

Improve glucose-dependent insulin secretion, slow gastric emptying time, reduce food intake by enhancing satiety (a feeling of fullness), decrease postprandial glucagon secretion, and promote ß-cell proliferation. Consequently, postprandial hyperglycemia is reduced, AIC levels decrease, and weight loss may occur

Administered subcutaneously, since they are polypeptides. Dulaglutide, liraglutide, and semaglutide are considered long-acting GLP-I receptor agonists. Dulaglutide and semaglutide are dosed once weekly, while liraglutide is available as a once-daily injection. The oral formulation of semaglutide is dosed once daily. Lixisenatide is a short-acting GLP-I receptor agonist that is dosed once daily. Exenatide is available as both a short-acting (dosed twice daily) and extended-release preparation (dosed once weekly). Exenatide should be avoided in patients with severe renal impairment.

Nausea, vomiting, diarrhea, and constipation. These agents have been associated with pancreatitis and should be avoided in patients with chronic pancreatitis. Longer-acting agents have been associated with thyroid C-cell tumors in rodents. It is unknown if GLP-I receptor agonists cause these tumors or thyroid carcinoma in humans although they are contraindicated in patients with a history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.

Amylin is a hormone that is co-secreted with insulin from ß cells following food intake. It delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety. Pramlintide is a synthetic amylin analog that is indicated as an adjunct to mealtime insulin in patients with type I and type 2 diabetes. Pramlintide is administered by subcutaneous injection immediately before meals. When pramlintide is initiated, the dose of mealtime insulin should be decreased by 50% to avoid a risk of severe hypoglycemia. Other adverse effects include nausea, anorexia, and vomiting. Pramlintide may not be mixed in the same syringe with insulin, and it should be avoided in patients with diabetic gastroparesis (delayed stomach emptying), cresol hypersensitivity, or hypoglycemic unawareness.

Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are oral sodium—glucose cotransporter 2 inhibitors for the treatment of type 2 diabetes. Canagliflozin and empagliflozin are also indicated to reduce the risk of cardiovascular death in patients with type 2 diabetes and cardiovascular disease. In addition, canagliflozin and dapagliflozin have been shown to reduce the risk of heart failure hospitalizations and end-stage kidney disease in patients with type 2 diabetes.

Reabsorbing filtered glucose in the tubular lumen of the kidney. By inhibiting SGLT2, these agents decrease reabsorption of glucose, increase urinary glucose excretion, and lower blood glucose. Inhibition of SGLT2 also decreases reabsorption of sodium and causes osmotic diuresis.

Dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide

Pramlintide

Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin

These agents are given once daily in the morning. Canagliflozin should be taken before the first meal of the day. All drugs are mainly metabolized by glucuronidation to inactive metabolites. These agents should be avoided in patients with severe renal dysfunction.

Female genital mycotic infections (for example, vulvovaginal candidiasis), urinary tract infections, and urinary frequency. Hypotension has also occurred, particularly in the elderly or patients on diuretics. Thus, volume status should be evaluated prior to starting these agents. Ketoacidosis has been reported with use of SGLT2 inhibitors, and these agents should be used with caution in patients with risk factors that predispose to ketoacidosis (for example, alcohol abuse and caloric restriction related to surgery or illness). SGLT2 inhibitors are also associated with an increased risk of bone fractures and Fournier gangrene.

Dopamine Agonist (Cycloset)

Bile Acid Sequestrants (Colesevelam)

-Using a combination of treatments (ie, an oral medication plus insulin) generally lowers the dose of insulin compared with taking insulin only -Since insulin can cause weight gain, combination therapy may reduce the risk of weight gain

All above and below

continue the glargine and take lispro only as a supplement

eliminate the snack

Glyburide

Gastrointestinal upset

ALT

Postprandial hyperglycemia