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ADA 23 > 9. Pharmacologic Approaches 23 > Flashcards

9. Pharmacologic Approaches 23 Flashcards

1
Q

What are two pharmacologic approaches that may help improve blood glucose control and reduce the amount of insulin needed?

A

The adjunctive use of a thiazolidinedione and an SGLT2 inhibitor.

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2
Q

When initiating combination injectable therapy, which medication is typically maintained?

A

Metformin therapy is typically maintained….
sulfonylureas and DPP-4 inhibitors are typically weaned or discontinued.

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3
Q

What is one way to intensify insulin treatment?

A

One way to intensify insulin treatment is by adding doses of prandial insulin to basal insulin.

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4
Q

What is the suggested starting point for adding prandial insulin to basal insulin?

A

The suggested starting point for adding prandial insulin to basal insulin is starting with a single prandial dose with the largest meal of the day.

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5
Q

What are the two available options of basal insulin plus a GLP-1 RA?

A

The two available options are insulin glargine plus lixisenatide (iGlarLixi) and insulin degludec plus liraglutide (IDegLira).

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6
Q

What did the DUAL VIII trial demonstrate?

A

The DUAL VIII trial demonstrated greater durability of glycemic treatment effect with the combination GLP-1 RA–insulin therapy compared with addition of basal insulin alone.

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7
Q

What is the name of the trial that demonstrated greater durability of glycemic treatment effect?

A

The trial is called DUAL VIII (Durability of Insulin Degludec Plus Liraglutide Versus Insulin Glargine U100 as Initial Injectable Therapy in Type 2 Diabetes) randomized controlled trial.

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8
Q

What are the advantages of combining basal insulin and GLP-1 RA for glycemic treatment?

A

The combination of basal insulin and GLP-1 RA has potent glucose-lowering actions and less weight gain and hypoglycemia compared with intensified insulin regimens.

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9
Q

How does the combination of basal insulin and GLP-1 RA compare to intensified insulin regimens in terms of weight gain and hypoglycemia?

A

The combination of basal insulin and GLP-1 RA has less weight gain and hypoglycemia compared with intensified insulin regimens.

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10
Q

When should combination injectable therapy be considered?

A

Combination injectable therapy should be considered if basal insulin has been titrated to an acceptable fasting blood glucose level (or if the dose is >0.5 units/kg/day with indications of need for other therapy) and A1C remains above target.

a GLP-1 RA or dual GIP and GLP-1 RA added to basal insulin or multiple doses of insulin

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11
Q

What are the contraindications for inhaled insulin?

A

Inhaled insulin is contraindicated in individuals with chronic lung disease, such as asthma and chronic obstructive pulmonary disease, and is not recommended in individuals who smoke or who recently stopped smoking.

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12
Q

What testing is required before and after starting inhaled insulin therapy?

A

All individuals require spirometry (FEV1) testing to identify potential lung disease prior to and after starting inhaled insulin therapy.

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13
Q

What potential side effect may occur with the use of inhaled insulin?

A

The use of inhaled insulin may result in a decline in lung function (reduced forced expiratory volume in 1 s [FEV1]).

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14
Q

How does inhaled insulin compare to injectable insulin in terms of onset and duration?

A

Inhaled insulin has a faster onset and shorter duration compared to injectable insulin.

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15
Q

What are the advantages of inhaled insulin over injectable insulin?

A

Inhaled insulin has demonstrated clinically meaningful A1C reductions and weight reductions compared to injectable insulin aspart over a period of 24 weeks.

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16
Q

How is U-500 regular insulin available?

A

U-500 regular insulin is available in both prefilled pens and vials.
RAA ONLY PENS

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17
Q

What is the benefit of using concentrated formulations of insulin?

A

The benefit of using concentrated formulations of insulin is that they are more convenient and comfortable to inject, and may improve treatment plan engagement for individuals with insulin resistance who require large doses of insulin.

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18
Q

What are the two concentrated formulations of rapid-acting insulin lispro that have been approved by the FDA?

A

The two concentrated formulations of rapid-acting insulin lispro that have been approved by the FDA are U-200 (200 units/mL) and insulin lispro-aabc (U-200).

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19
Q

How does the duration of action of U-300 glargine compare to U-100 glargine?

A

U-300 glargine has a longer duration of action than U-100 glargine.
but modestly lower efficacy per unit administered

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20
Q

What are the concentrations of U-300 glargine and U-200 degludec compared to their U-100 formulations?

A

U-300 glargine is three times as concentrated as U-100 glargine, and U-200 degludec is two times as concentrated as U-100 degludec.

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21
Q

What advantage do U-300 glargine and U-200 degludec offer in terms of insulin administration?

A

U-300 glargine and U-200 degludec allow higher doses of basal insulin administration per volume used.

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22
Q

What are the pharmacokinetic characteristics of U-500 regular insulin?

A

U-500 regular insulin has delayed onset and longer duration of action, similar to intermediate-acting (NPH) insulin.

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23
Q

How can U-500 regular insulin be used?

A

U-500 regular insulin can be used as two or three daily injections.

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24
Q

In trials comparing rapid-acting insulin analogs with human regular insulin in type 2 diabetes, what important differences have meta-analyses not reported regarding A1C and hypoglycemia?

A

Meta-analyses have not reported important differences in A1C or hypoglycemia.

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25
Q

What did meta-analyses of trials comparing rapid-acting insulin analogs with human regular insulin in type 2 diabetes find regarding A1C and hypoglycemia?

A

Meta-analyses have not reported important differences in A1C or hypoglycemia.

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26
Q

Are individuals with type 2 diabetes generally more insulin resistant than those with type 1 diabetes?

A

Yes, individuals with type 2 diabetes are generally more insulin resistant than those with type 1 diabetes.

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27
Q

What daily doses of insulin are required for individuals with type 2 diabetes?

A

Individuals with type 2 diabetes generally require higher daily doses, approximately 1 unit/kg.

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28
Q

What is the recommended estimate for initiating prandial insulin therapy?

A

A prandial insulin dose of 4 units or 10% of the amount of basal insulin at the largest meal or the meal with the greatest postprandial excursion.

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29
Q

What are some clinical signals that may prompt evaluation of overbasalization?

A

Some clinical signals that may prompt evaluation of overbasalization include basal dose greater than ∼0.5 units/kg, high bedtime–morning or postpreprandial glucose differential, hypoglycemia (aware or unaware), and high variability.

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30
Q

When should reevaluation of therapy be prompted?

A

Reevaluation of therapy should be prompted when there is an indication of overbasalization, in order to further individualize therapy.

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31
Q

Compared to NPH insulin, what has been demonstrated in relation to the risk of symptomatic and nocturnal hypoglycemia with long-acting basal analogs?

A

Long-acting basal analogs (U-100 glargine or detemir) have been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia.

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32
Q

Which types of long-acting basal analogs have been shown to reduce the risk of symptomatic and nocturnal hypoglycemia?

A

U-100 glargine or detemir

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33
Q

What is the principal action of basal insulin?

A

The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals.

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34
Q

What is the recommended starting dose for basal insulin?

A

The recommended starting dose for basal insulin can be estimated based on body weight (0.1–0.2 units/kg/day) and the degree of hyperglycemia.

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35
Q

What is the benefit of combination therapy with a GLP-1 RA in individuals intensified to insulin therapy?

A

Combination therapy with a GLP-1 RA has shown greater efficacy and durability of glycemic treatment effect, as well as weight and hypoglycemia benefit, compared to treatment intensification with insulin alone.

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36
Q

What does GLP-1 RA stand for in the context of glycemic treatment?

A

GLP-1 RA stands for Glucagon-Like Peptide-1 Receptor Agonist.

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37
Q

In clinical trials comparing injectable GLP-1 RA with basal insulin, what was found regarding their glycemic efficacy?

A

The glycemic efficacy of injectable GLP-1 RA was similar or greater than that of basal insulin.

LESS HYPOA
LOWER WEIGHT

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38
Q

Approximately how much does each new class of noninsulin agents added to initial therapy with metformin lower A1C?

A

Each new class of noninsulin agents added to initial therapy with metformin generally lowers A1C approximately 0.7–1.0%.

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39
Q

What are some important clinical characteristics to consider when determining pharmacologic approaches to glycemic treatment?

A

Important clinical characteristics include the presence of established ASCVD or indicators of high ASCVD risk, HF, CKD, obesity, nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, and risk for specific adverse drug effects, as well as safety.

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40
Q

What are some specific indicators of high ASCVD risk that should be considered when determining pharmacologic approaches to glycemic treatment?

A

Specific indicators of high ASCVD risk should be considered when determining pharmacologic approaches to glycemic treatment.

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41
Q

What is the name of the trial that demonstrated the superiority of initial combination therapy?

A

The trial is called VERIFY (Vildagliptin Efficacy in combination with metfoRmln For earlY treatment of type 2 diabetes) trial.

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42
Q

What is the benefit of initial combination therapy?

A

Initial combination therapy allows for more rapid attainment of glycemic goals.

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43
Q

What can often be possible as glucose toxicity resolves AFTER INITIAL INSULIN THERAPY?

A

Simplifying the regimen and/or changing to noninsulin agents.

44
Q

What is the recommended treatment approach when A1C is ≥1.5% (12.5 mmol/mol) above the glycemic target?

A

When A1C is ≥1.5% (12.5 mmol/mol) above the glycemic target, many individuals will require dual-combination therapy or a more potent glucose-lowering agent to achieve and maintain their target A1C level.

45
Q

According to the DPPOS study, what does periodic testing of vitamin B12 suggest?

A

Periodic testing of vitamin B12 suggests

46
Q

What modification has the FDA made to the metformin label?

A

The FDA has revised the label for metformin to reflect its safety in people with eGFR ≥30 mL/min/1.73 m.

47
Q

Compared to sulfonylureas, what are the beneficial effects of metformin as first-line therapy?

A

Metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality compared to sulfonylureas.

48
Q

Which two medications have shown very high efficacy for weight loss?

A

Semaglutide and tirzepatide

49
Q

When should pharmacotherapy be started for type 2 diabetes?

A

Pharmacotherapy should be started at the time type 2 diabetes is diagnosed unless there are contraindications.

50
Q

What are some clinical signals that may prompt evaluation of overbasalization?

A

Some clinical signals that may prompt evaluation of overbasalization include basal dose more than ∼0.5 units/kg/day, high bedtime–morning or postpreprandial glucose differential, hypoglycemia (aware or unaware), and high glycemic variability.

51
Q

What should clinicians do if there is an indication of overbasalization?

A

If there is an indication of overbasalization, clinicians should prompt reevaluation to further individualize therapy.

52
Q

How often should medication regimen and medication-taking behavior be reevaluated?

A

Medication regimen and medication-taking behavior should be reevaluated at regular intervals every 3–6 months.

53
Q

What factors should be considered when adjusting the medication regimen?

A

Specific factors that impact choice of treatment should be incorporated when adjusting the medication regimen.

54
Q

According to the content, what is the recommendation for treatment intensification?

A

The recommendation for treatment intensification for individuals not meeting treatment goals should not be delayed.

55
Q

What is the recommended combination therapy for insulin usage?

A

Combination therapy with a glucagon-like peptide 1 receptor agonist.

56
Q

What are the benefits of combining a glucagon-like peptide 1 receptor agonist with insulin?

A

Greater efficacy, durability of treatment effect, and weight and hypoglycemia benefit.

57
Q

What is the preferred treatment option for adults with type 2 diabetes, instead of insulin?

A

A glucagon-like peptide 1 receptor agonist is preferred.

58
Q

When should the early introduction of insulin be considered?

A

The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when A1C levels (>10% [86 mmol/mol]) or blood glucose levels (≥300 mg/dL [16.7 mmol/L]) are very high.

59
Q

When can early combination therapy be considered?

A

Early combination therapy can be considered in some individuals at treatment initiation to extend the time to treatment failure.

60
Q

Should metformin be continued when starting insulin therapy?

A

Metformin should be continued upon initiation of insulin therapy (unless contraindicated or not tolerated) for ongoing glycemic and metabolic benefits.

61
Q

Why is weight management considered an impactful component of glucose-lowering management in type 2 diabetes?

A

Weight management is considered impactful because it supports the goals of glucose-lowering treatment regimen.

62
Q

What are some pharmacologic approaches to achieve and maintain treatment goals for diabetes?

A

Some pharmacologic approaches include metformin or other agents, including combination therapy.

63
Q

What conditions should be present in adults with type 2 diabetes for the treatment regimen to include agents that reduce cardiorenal risk?

A

Established/high risk of atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease.

64
Q

What factors should guide the pharmacologic therapy for adults with Type 2 Diabetes?

A

Person-centered treatment factors, comorbidities, and treatment goals should guide the pharmacologic therapy for adults with Type 2 Diabetes.

65
Q

What are some important considerations in the glucose-lowering management of Type 2 Diabetes?

A

Some important considerations in the glucose-lowering management of Type 2 Diabetes include healthy lifestyle behaviors, diabetes self-management education and support, avoidance of clinical inertia, and social determinants of health.

66
Q

What is the overall recommendation for the glucose-lowering management of Type 2 Diabetes?

A

The overall recommendation for the glucose-lowering management of Type 2 Diabetes is to consider healthy lifestyle behaviors, diabetes self-management education and support, avoidance of clinical inertia, and social determinants of health, while also guiding pharmacologic therapy based on person-centered treatment factors, comorbidities, and treatment goals.

67
Q

For whom should pancreas transplantation be reserved?

A

Pancreas transplantation should be reserved for people with type 1 diabetes undergoing simultaneous renal transplantation, following renal transplantation, or for those with recurrent ketoacidosis or severe hypoglycemia despite intensive glycemic management.

68
Q

What is the association between SGLT2 inhibitor use and type 1 diabetes?

A

SGLT2 inhibitor use in type 1 diabetes is associated with an increased rate of diabetic ketoacidosis.

69
Q

What are the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in people with type 1 diabetes? DEPICT-1TRIAL

A

SGLT2 inhibitors have shown improvements in A1C levels, reduced body weight, and improved blood pressure in clinical trials.

70
Q

What type of diabetes were sodium-glucose cotransporter 2 (SGLT2) inhibitors studied in?DEPICT-1 TRIAL?

A

SGLT2 inhibitors were studied in people with type 1 diabetes in clinical trials.

71
Q

What are the key findings of the largest clinical trials{ ADJUNCT ONE ) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in type 1 diabetes with liraglutide 1.8 mg daily?

A

The key findings include modest A1C reductions of approximately 0.4%, decreases in weight of approximately 5 kg, and reductions in insulin doses.

72
Q

What were the effects of adding metformin in adults with type 1 diabetes?

A

The addition of metformin in adults with type 1 diabetes caused small reductions in body weight and lipid levels but did not improve A1C.

73
Q

What is the primary objective that was not achieved by adding metformin in adults with type 1 diabetes?

A

The addition of metformin in adults with type 1 diabetes did not improve A1C.

74
Q

What are the effects of pramlintide on A1C and weight?

A

Pramlintide leads to a modest reduction in A1C (0.3–0.4%) and modest weight loss (∼1 kg).

75
Q

What is Pramlintide?

A

Pramlintide is a medication based on the naturally occurring β-cell peptide amylin that is approved for use in adults with type 1 diabetes.

76
Q

Who is Pramlintide approved for?

A

Pramlintide is approved for use in adults with type 1 diabetes.

77
Q

What is lipohypertrophy?

A

Lipohypertrophy is an accumulation of subcutaneous fat in response to the adipogenic actions of insulin at a site of multiple injections.

78
Q

What are the effects of lipohypertrophy?

A

Lipohypertrophy can contribute to erratic insulin absorption, increased glycemic variability, and unexplained hypoglycemic episodes.

79
Q

What is the effect of injecting insulin into the limbs instead of truncal sites?

A

IM insulin delivery is increased in younger, leaner individuals when injecting into the limbs rather than truncal sites.

80
Q

What type of needles are recommended for insulin injection?

A

Recent evidence supports the use of short needles (e.g., 4-mm pen needles).

81
Q

Why is IM injection associated with frequent and unexplained hypoglycemia?

A

IM injection can lead to unpredictable insulin absorption and variable effects on glucose.

82
Q

What are the potential effects of IM injection on glucose levels?

A

Variable effects on glucose.

83
Q

Should exogenously delivered insulin be injected intramuscularly?

A

No, exogenously delivered insulin should be injected into subcutaneous tissue, not intramuscularly.

84
Q

What can be incorporated into prandial dosing for individuals who find carbohydrate counting effective?

A

Estimates of the fat and protein content of meals.

85
Q

What is the potential benefit of incorporating estimates of fat and protein content into prandial dosing for individuals who find carbohydrate counting effective?

A

Added benefit.

86
Q

What factors determine the optimal time to administer prandial insulin?

A

The optimal time to administer prandial insulin varies based on the pharmacokinetics of the formulation, premeal blood glucose level, and carbohydrate consumption.

87
Q

How can total daily insulin requirements be estimated?T1DM

A

Total daily insulin requirements can be estimated based on weight….s ranging from 0.4 to 1.0 units/kg/day. Higher amounts are required during puberty, pregnancy, and medical illness.

88
Q

In the iDCL trial, what were the benefits associated with the use of a closed-loop system compared to a sensor-augmented pump?

A

The benefits associated with the use of a closed-loop system in the iDCL trial were a greater percentage of time spent in the target glycemic range, reduced mean glucose and A1C levels, and a lower percentage of time spent in hypoglycemia.

The iDCL trial had a duration of 6 months.

89
Q

Over what duration was the comparison conducted to determine the superiority of closed-loop system over sensor-augmented pump therapy?

A

3 months

90
Q

What are hybrid closed-loop pump systems also known as?

A

Hybrid closed-loop pump systems are also known as automated insulin delivery (AID) systems.

91
Q

What organization has approved multiple hybrid closed-loop pump systems?

A

The U.S. Food and Drug Administration (FDA) has approved multiple hybrid closed-loop pump systems.

92
Q

How can the reduction of nocturnal hypoglycemia be improved in individuals with type 1 diabetes?

A

The reduction of nocturnal hypoglycemia in individuals with type 1 diabetes can be improved by automatic suspension of insulin delivery at a preset glucose level.

93
Q

What does a systematic review and meta-analysis conclude about CSII via pump therapy?

A

A systematic review and meta-analysis concluded that CSII via pump therapy has modest advantages for lowering A1C (−0.30% [95% CI −0.58 to −0.02]) and for reducing severe hypoglycemia rates in children and adults.

94
Q

Compared to U-100 glargine, do longer-acting basal analogs (U-300 glargine or degludec) pose a lower risk of hypoglycemia?

A

Yes, longer-acting basal analogs (U-300 glargine or degludec) may confer a lower hypoglycemia risk compared with U-100 glargine in individuals with type 1 diabetes.

95
Q

According to the content, which insulins may reduce prandial excursions better than RAA?

A

Ster-acting insulin aspart and insulin lispro-aabc may reduce prandial excursions better than RAA.

96
Q

What are the potential benefits of inhaled human insulin compared to RAA?

A

Inhaled human insulin may cause less hypoglycemia and weight gain compared to RAA.

97
Q

What are the advantages of treatment with analog insulins in people with type 1 diabetes?

A

Treatment with analog insulins is associated with less hypoglycemia and weight gain as well as lower A1C compared with human insulins.

98
Q

What percentage of reduction in microvascular complications was observed after 6 years of treatment with intensive control? DCCT TRIAL

A

Around 50% reductions in microvascular complications were observed after 6 years of treatment with intensive control.

99
Q

What did the Diabetes Control and Complications Trial (DCCT) demonstrate?

A

The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy with multiple daily injections or continuous subcutaneous insulin infusion (CSII) reduced A1C and was associated with improved long-term outcomes.

100
Q

What is the recommended pharmacologic therapy for adults with Type 1 Diabetes?

A

Most individuals with Type 1 Diabetes should be treated with multiple daily injections of prandial and basal insulin, or continuous subcutaneous insulin infusion.

101
Q

What type of insulin should most individuals with Type 1 Diabetes use to reduce the risk of hypoglycemia?

A

Most individuals with Type 1 Diabetes should use rapid-acting insulin analogs to reduce hypoglycemia risk.

102
Q

What education should individuals with Type 1 Diabetes receive regarding mealtime insulin doses?

A

Individuals with Type 1 Diabetes should receive education on how to match mealtime insulin doses to carbohydrate intake, fat and protein content, and anticipated physical activity.

103
Q

Algorithm transplant

A
104
Q

Algorithm type 2 DM

A
105
Q

TABLE MEDICATIONS

A
106
Q

INSULIN ALGORITHM

A

ADA 23 (9 decks)

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