If your A1c is under 7.5%, you could technically use 1 drug. If it is a post-meal problem, use an incretin mimetic or something similar. If the A1c is just under 7.5% and there is a high fasting, use 1 drug to treat that such as metformin.
The ADA suggests maintaining FBG values between 70 and 130 mg/dL and peak post-prandial glucose (PPG) -- 1 to 2 hours following the meal -- values below 180 mg/dL in order to achieve an A1c goal of less than 7%.
Alternatively, the American Association of Clinical Endocrinologists (AACE) recommends a lower A1c target of 6.5%, by maintaining FBG below 110 mg/dL and 2-hour PPG levels below 140 mg/dL. Target A1c levels need to be determined on the basis on several factors, including hypoglycemia risk and vulnerability.
The usual approach in insulin initiation has been the “Fix Fasting First” approach; this is achieved through the use of appropriate basal insulin replacement (usually with basal insulin doses ranging between 0.4 and 0.6 units/kg/day) and the subsequent addition -- if A1c levels remain above target -- of 1 or more doses of a rapid-acting insulin analog added to 1 or more meals in a sequential manner.
Specifically, 4 to 6 units of a rapid-acting analog are added before the main (largest) meal of the day and titrated to either 2-hour PPG (blood glucose < 180 mg/dL) or next preprandial (blood glucose < 130 mg/dL) targets. On average, 8 to 12 units of rapid-acting insulin are needed to adequately control PPG in the average 100-kg patient with type 2 diabetes. If full basal/bolus insulin therapy is needed in patients with type 2 diabetes, then fixed doses of premeal insulin appear to have similar effectiveness and safety as compared to more complex approaches that require matching insulin to carbohydrates or using frequent supplemental scale corrections.
An alternative approach to controlling prandial glycemia, while potentially minimizing both weight gain and hypoglycemia risk, is the use of incretin-based drugs[36] either alone or in combination with basal insulin. Because these pharmacotherapies exert their effect on β-cells (stimulating insulin secretion and release or suppressing glucagon release) in a glucose-dependent manner, they are associated with a low risk for hypoglycemia when used without hypoglycemic agents (eg, sulfonylureas, glinides, insulin).
The 2 major classes of incretin drugs available for clinical use in the United States are dipeptidyl peptidase (DPP)-4 inhibitors (ie, sitagliptin, saxagliptin, linagliptin) and glucagon-like peptide (GLP)-1 receptor agonists (ie, exenatide, liraglutide).
On average, DPP-4 inhibitors lower A1c levels less -- decrease of 0.5% to 0.8% -- than GLP-1 receptor agonists -- decrease of 0.6% to 1.9%. GLP-1 receptor agonists can be further subdivided into short-acting (exenatide) and long-acting (liraglutide long-acting release and exenatide long-acting release) agonists.
On average, short-acting GLP-1 receptor agonists tend to lower PPG more effectively than long-acting GLP-1 receptor agonists, while long-acting GLP-1 receptor agonists have a greater impact on fasting plasma glucose.
PPG levels apparently have a better correlation with A1c than do fasting blood glucose (FBG) levels, especially when the A1c is less than 8.4%. Furthermore, reduced early and “first-phase” insulin releases, fundamental defects in type 2 diabetes, lead to high PPG levels. Insulin resistance and the reduced incretin effect in type 2 diabetes also contribute significantly to postprandial hyperglycemia.
The DCCT/EDIC trial reported a macrovascular benefit in the original intensively controlled group despite subsequent loss of A1c control equivalent to the post DCCT conventionally treated group. This important concept, termed “metabolic memory,” provides evidence supporting the importance of early, aggressive control of diabetes. Additionally, evidence from the Kumamoto Study and the United Kingdom Prospective Diabetes Study confirm reduced microvascular complications with lower A1c levels.
Strong epidemiologic evidence from varied populations links post-challenge hyperglycemia to macrovascular complications; these studies include the Rancho Bernardo Study, the Honolulu Heart Study, the Paris Prospective Heart Study, the Diabetes Intervention Study, and the Diabetes Epidemiology:Collaborative Analysis of Diagnostic Criteria in Europe Study.
Possible effects of acute hyperglycemia responsible for increased microvascular and macrovascular risk include:
In 2003, Monnier and colleagues demonstrated that, in patients with an A1c level less than 7.3%, reductions in postprandial glycemia were approximately 70% responsible for the improvement in glycemic control as measured by A1c. Whereas for patients with an A1c greater than 8.0%, improvements in fasting glycemic control contributed more to the overall glycemic control than did postprandial glycemia. This observation, practically stated, supports the “Fix Fasting First” approach commonly used in clinical practice.
In 2007, Monnier and colleagues designed a study in early diabetes to demonstrate that the loss of glycemic control progressed sequentially from postprandial to fasting. In this study, the researchers found that the initial differences in mean glucose concentrations reached statistical significance during daytime postprandial periods first, followed by morning periods (otherwise known as the dawn phenomenon), and then nocturnal fasting periods. The finding led Monnier and his team to conclude that the deterioration in glucose control progressed stepwise in the 3 postmeal periods leading to fasting hyperglycemia; this observation, therefore, supports a stepwise treatment program and medication titration.
In the appropriate patients, as determined by their fasting blood glucose (FBG) and A1c, a clinician can effectively titrate treatment to achieve FBG in the target (100 to 126 mg/dL) range. If the A1c remains above the target, then management of the postprandial blood glucose component becomes essential to improve glycemic control.
In a more recent study, Monnier and colleagues suggest that, to achieve glycemic targets less than 6.5% (as currently recommended by ACE/AACE and the International Diabetes Federation), attention must be paid to the PPG. However, there is a caveat to take into consideration: Riddle and colleagues recently published a study evaluating PPG and from their data, it can be concluded that contribution of PPG and fasting plasma glucose depends on treatment.
If the FBG has been optimized or treated to the target and the A1c is still not at goal, targeting the PPG is the next step. A reasonable approach is to start with the largest meal first (typically dinner) and measure the blood glucose 2 hours after the beginning of the meal. Different organizations have proposed different targets.
The ADA suggests maintaining FBG values between 70 and 130 mg/dL and peak post-prandial glucose (PPG) -- 1 to 2 hours following the meal -- values below 180 mg/dL in order to achieve an A1c goal of less than 7%.
Alternatively, the American Association of Clinical Endocrinologists (AACE) recommends a lower A1c target of 6.5%, by maintaining FBG below 110 mg/dL and 2-hour PPG levels below 140 mg/dL. Target A1c levels need to be determined on the basis on several factors, including hypoglycemia risk and vulnerability.
The usual approach in insulin initiation has been the “Fix Fasting First” approach; this is achieved through the use of appropriate basal insulin replacement (usually with basal insulin doses ranging between 0.4 and 0.6 units/kg/day) and the subsequent addition -- if A1c levels remain above target -- of 1 or more doses of a rapid-acting insulin analog added to 1 or more meals in a sequential manner.
Specifically, 4 to 6 units of a rapid-acting analog are added before the main (largest) meal of the day and titrated to either 2-hour PPG (blood glucose < 180 mg/dL) or next preprandial (blood glucose < 130 mg/dL) targets. On average, 8 to 12 units of rapid-acting insulin are needed to adequately control PPG in the average 100-kg patient with type 2 diabetes. If full basal/bolus insulin therapy is needed in patients with type 2 diabetes, then fixed doses of premeal insulin appear to have similar effectiveness and safety as compared to more complex approaches that require matching insulin to carbohydrates or using frequent supplemental scale corrections.
An alternative approach to controlling prandial glycemia, while potentially minimizing both weight gain and hypoglycemia risk, is the use of incretin-based drugs[36] either alone or in combination with basal insulin. Because these pharmacotherapies exert their effect on β-cells (stimulating insulin secretion and release or suppressing glucagon release) in a glucose-dependent manner, they are associated with a low risk for hypoglycemia when used without hypoglycemic agents (eg, sulfonylureas, glinides, insulin).
The 2 major classes of incretin drugs available for clinical use in the United States are dipeptidyl peptidase (DPP)-4 inhibitors (ie, sitagliptin, saxagliptin, linagliptin) and glucagon-like peptide (GLP)-1 receptor agonists (ie, exenatide, liraglutide).
On average, DPP-4 inhibitors lower A1c levels less -- decrease of 0.5% to 0.8% -- than GLP-1 receptor agonists -- decrease of 0.6% to 1.9%. GLP-1 receptor agonists can be further subdivided into short-acting (exenatide) and long-acting (liraglutide long-acting release and exenatide long-acting release) agonists.
On average, short-acting GLP-1 receptor agonists tend to lower PPG more effectively than long-acting GLP-1 receptor agonists, while long-acting GLP-1 receptor agonists have a greater impact on fasting plasma glucose.
PPG levels apparently have a better correlation with A1c than do fasting blood glucose (FBG) levels, especially when the A1c is less than 8.4%. Furthermore, reduced early and “first-phase” insulin releases, fundamental defects in type 2 diabetes, lead to high PPG levels. Insulin resistance and the reduced incretin effect in type 2 diabetes also contribute significantly to postprandial hyperglycemia.
The DCCT/EDIC trial reported a macrovascular benefit in the original intensively controlled group despite subsequent loss of A1c control equivalent to the post DCCT conventionally treated group. This important concept, termed “metabolic memory,” provides evidence supporting the importance of early, aggressive control of diabetes. Additionally, evidence from the Kumamoto Study and the United Kingdom Prospective Diabetes Study confirm reduced microvascular complications with lower A1c levels.
Strong epidemiologic evidence from varied populations links post-challenge hyperglycemia to macrovascular complications; these studies include the Rancho Bernardo Study, the Honolulu Heart Study, the Paris Prospective Heart Study, the Diabetes Intervention Study, and the Diabetes Epidemiology:Collaborative Analysis of Diagnostic Criteria in Europe Study.
Possible effects of acute hyperglycemia responsible for increased microvascular and macrovascular risk include:
- Endothelial dysfunction
- Increased oxidative load
- A pro-inflammatory state
- Protein glycosylation
- Altered coagulation
In 2007, Monnier and colleagues designed a study in early diabetes to demonstrate that the loss of glycemic control progressed sequentially from postprandial to fasting. In this study, the researchers found that the initial differences in mean glucose concentrations reached statistical significance during daytime postprandial periods first, followed by morning periods (otherwise known as the dawn phenomenon), and then nocturnal fasting periods. The finding led Monnier and his team to conclude that the deterioration in glucose control progressed stepwise in the 3 postmeal periods leading to fasting hyperglycemia; this observation, therefore, supports a stepwise treatment program and medication titration.
In the appropriate patients, as determined by their fasting blood glucose (FBG) and A1c, a clinician can effectively titrate treatment to achieve FBG in the target (100 to 126 mg/dL) range. If the A1c remains above the target, then management of the postprandial blood glucose component becomes essential to improve glycemic control.
In a more recent study, Monnier and colleagues suggest that, to achieve glycemic targets less than 6.5% (as currently recommended by ACE/AACE and the International Diabetes Federation), attention must be paid to the PPG. However, there is a caveat to take into consideration: Riddle and colleagues recently published a study evaluating PPG and from their data, it can be concluded that contribution of PPG and fasting plasma glucose depends on treatment.
If the FBG has been optimized or treated to the target and the A1c is still not at goal, targeting the PPG is the next step. A reasonable approach is to start with the largest meal first (typically dinner) and measure the blood glucose 2 hours after the beginning of the meal. Different organizations have proposed different targets.
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