A Closer Look Inside Healthy Eating Patterns
Unlike aspartame, sucralose does not break down at high temperatures and so can be used in baked goods. Autolyzed yeast extract is sometimes used to substitute for MSG, but has much lower levels of glutamate so adverse reactions are unlikely. Push the Dose Knob all the way in. Stroke fatal or nonfatal. It provides regulations on what, where, and how prominently information should be placed on packaging. Dozens of drugs were eventually suspended or recalled by manufacturers.
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Choices within these eating patterns may include processed meats and processed poultry as long as the resulting eating pattern is within limits for sodium, calories from saturated fats and added sugars, and total calories.
Oils are fats that contain a high percentage of monounsaturated and polyunsaturated fats and are liquid at room temperature. Although they are not a food group, oils are emphasized as part of healthy eating patterns because they are the major source of essential fatty acids and vitamin E. Commonly consumed oils extracted from plants include canola, corn, olive, peanut, safflower, soybean, and sunflower oils. Oils also are naturally present in nuts, seeds, seafood, olives, and avocados.
The fat in some tropical plants, such as coconut oil, palm kernel oil, and palm oil, are not included in the oils category because they do not resemble other oils in their composition. Specifically, they contain a higher percentage of saturated fats than other oils see Dietary Fats: The Basics call-out box. The recommendation for oils in the Healthy U.
Oils are part of healthy eating patterns, but because they are a concentrated source of calories, the amount consumed should be within the AMDR for total fats without exceeding calorie limits. Oils should replace solid fats rather than being added to the diet. More information on types of fats is provided in the Dietary Fats: The Basics call-out box, and information on the relationship between dietary fats and health is discussed in the Saturated Fats, Trans Fats, and Cholesterol section, below.
Dietary fats are found in both plant and animal foods. They supply calories and help with the absorption of the fat-soluble vitamins A, D, E, and K. All dietary fats are composed of a mix of polyunsaturated, monounsaturated, and saturated fatty acids, in varied proportions Figure For example, most of the fatty acids in butter are saturated, but it also contains some monounsaturated and polyunsaturated fatty acids.
Oils are mostly unsaturated fatty acids, though they have small amounts of saturated fatty acids. Figure is a stacked bar chart depicting the fatty acid composition as a percent of total fat of saturated, monounsaturated, and polyunsaturated solid fats and oils. Fats and oils are listed in order of highest to lowest percent of saturated fats. However, they are solid or semi-solid at room temperature due to their high content of short-chain saturated fatty acids.
They are considered solid fats for nutritional purposes. Accessed August 31, Some solid fats, such as the strip of fat around a piece of meat, can easily be seen. Other solid fats are not so visible. For example, the solid fats in whole milk are suspended in the fluid milk by the process of homogenization. Margarines and margarine-like vegetable oil spreads are food products composed of one or more oils or solid fats designed to replace butter, which is high in saturated fats.
These products may be sold in sticks, tubs, bottles, or sprays. Margarine and vegetable oil spreads generally contain less saturated fats than butter. However, they vary in their total fat and calorie content and in the fat and oil blends used to make them and, thus, in the proportions of saturated, unsaturated, and trans fats they contain. It is important to read the Nutrition Facts label to identify the calorie and saturated and trans fats content of the spread and choose foods with no trans fats and lower amounts of saturated fats.
The Dietary Guidelines provides recommendations on saturated fats as well as on solid fats because its aim is to improve the health of the U. It includes recommendations on saturated fats because of the strong relationship of this nutrient to a health outcome CVD risk.
It includes recommendations on solid fats because, as discussed in Chapter 2 , they are abundant in the diets of the U. The USDA Food Patterns are designed to meet food group and nutrient recommendations while staying within calorie needs. To achieve this goal, the Patterns are based on consuming foods in their nutrient-dense forms i.
For nearly all calorie levels, most of the calories in the USDA Food Patterns are needed for nutrient-dense food choices, and only a limited number remain for other uses. In the 2,calorie pattern, the limit for other uses is calories and in the 2,calorie pattern, calories see Appendix 3 , Appendix 4 , and Appendix 5. Calories up to the limit for the specific pattern can be used to eat foods that are not in nutrient-dense forms e. If alcohol is consumed, calories from alcoholic beverages should also be accounted for within this limit to keep total calorie intake at an appropriate level.
As discussed in Chapter 2 , in contrast to the healthy choices that make up the Patterns, foods from most food groups as they are typically consumed in the United States are not in nutrient-dense forms. The excess calories consumed from these sources far exceed the limited number of calories available for choices other than nutrient-dense foods in each food group.
From a public health perspective, it is important to identify the calories that are needed to meet food group needs to help inform guidance on limits from calories from added sugars, solid fats, alcohol  , or other sources, in order to help individuals move toward healthy eating patterns within calorie limits.
The USDA Food Patterns can be used to plan and serve meals for individuals, households, and in a variety of organizational settings e. The limit on calories for other uses can assist in determining how to plan and select foods that can fit within healthy eating patterns, such as how many calories are available to select foods from a food group that are not in nutrient-dense forms. As discussed in the next portion of the chapter, additional constraints apply related to other dietary components when building healthy eating patterns.
Many of the foods and beverages we eat contain sodium, saturated fats, and added sugars. Making careful choices, as in this example, keeps amounts of these components within their limits while meeting nutrient needs to achieve a healthy eating pattern.
Creamy peanut butter Sodium Saturated fats Added sugars. Mayonnaise Sodium Saturated fats. Spaghetti sauce Sodium Added sugars. Meatballs Sodium Saturated fats. Parmesan cheese Sodium Saturated fats. Ranch salad dressing Sodium Saturated fats Added sugars. In addition to the food groups, it is important to consider other food components when making food and beverage choices.
The components discussed below include added sugars, saturated fats, trans fats, cholesterol, sodium, alcohol, and caffeine. For each component, information is provided on how the component relates to eating patterns and outlines considerations related to the component.
See Chapter 2 for a further discussion of each of these components, current intakes, and shifts that are needed to help individuals align with a healthy eating pattern. Added sugars include syrups and other caloric sweeteners. When sugars are added to foods and beverages to sweeten them, they add calories without contributing essential nutrients.
Consumption of added sugars can make it difficult for individuals to meet their nutrient needs while staying within calorie limits. Naturally occurring sugars, such as those in fruit or milk, are not added sugars. Specific examples of added sugars that can be listed as an ingredient include brown sugar, corn sweetener, corn syrup, dextrose, fructose, glucose, high-fructose corn syrup, honey, invert sugar, lactose, malt syrup, maltose, molasses, raw sugar, sucrose, trehalose, and turbinado sugar.
Healthy eating patterns limit added sugars to less than 10 percent of calories per day. This recommendation is a target to help the public achieve a healthy eating pattern, which means meeting nutrient and food group needs through nutrient-dense food and beverage choices and staying within calorie limits. When added sugars in foods and beverages exceed 10 percent of calories, a healthy eating pattern may be difficult to achieve.
This target also is informed by national data on intakes of calories from added sugars, which as discussed in Chapter 2, account on average for almost calories, or more than 13 percent of calories per day in the U.
The USDA Food Patterns show that an eating pattern with enough foods from all food groups to meet nutrient needs without eating too many calories has only limited room for calories from added sugars.
At most lower calorie levels i. The recommendation to limit added sugars to no more than 10 percent of calories is a target that applies to all calorie levels to help individuals move toward healthy eating patterns within calorie limits. Although the evidence for added sugars and health outcomes is still developing, the recommendation to limit calories from added sugars is consistent with research examining eating patterns and health. Strong evidence from mostly prospective cohort studies but also randomized controlled trials has shown that eating patterns that include lower intake of sources of added sugars are associated with reduced risk of CVD in adults, and moderate evidence indicates that these eating patterns are associated with reduced risk of obesity, type 2 diabetes, and some types of cancer in adults.
Moderate evidence indicates a relationship between added sugars and dental caries in children and adults. As discussed in Chapter 2 , the two main sources of added sugars in U. Many foods high in calories from added sugars provide few or no essential nutrients or dietary fiber and, therefore, may contribute to excess calorie intake without contributing to diet quality; intake of these foods should be limited to help achieve healthy eating patterns within calorie limits.
There is room for Americans to include limited amounts of added sugars in their eating patterns, including to improve the palatability of some nutrient-dense foods, such as fruits and vegetables that are naturally tart e.
Healthy eating patterns can accommodate other nutrient-dense foods with small amounts of added sugars, such as whole-grain breakfast cereals or fat-free yogurt, as long as calories from added sugars do not exceed 10 percent per day, total carbohydrate intake remains within the AMDR, and total calorie intake remains within limits.
It should be noted that replacing added sugars with high-intensity sweeteners may reduce calorie intake in the short-term, yet questions remain about their effectiveness as a long-term weight management strategy. High-intensity sweeteners that have been approved by the U. This means that there is reasonable certainty of no harm under the intended conditions of use because the estimated daily intake is not expected to exceed the acceptable daily intake for each sweetener.
The FDA has determined that the estimated daily intake of these high-intensity sweeteners would not exceed the acceptable daily intake, even for high consumers of each substance.
Intake of saturated fats should be limited to less than 10 percent of calories per day by replacing them with unsaturated fats and while keeping total dietary fats within the age-appropriate AMDR.
The human body uses some saturated fats for physiological and structural functions, but it makes more than enough to meet those needs. Individuals 2 years and older therefore have no dietary requirement for saturated fats. Strong and consistent evidence shows that replacing saturated fats with unsaturated fats, especially polyunsaturated fats, is associated with reduced blood levels of total cholesterol and of low-density lipoprotein-cholesterol LDL-cholesterol.
Additionally, strong and consistent evidence shows that replacing saturated fats with polyunsaturated fats is associated with a reduced risk of CVD events heart attacks and CVD-related deaths. Some evidence has shown that replacing saturated fats with plant sources of monounsaturated fats, such as olive oil and nuts, may be associated with a reduced risk of CVD.
However, the evidence base for monounsaturated fats is not as strong as the evidence base for replacement with polyunsaturated fats. Evidence has also shown that replacing saturated fats with carbohydrates reduces blood levels of total and LDL-cholesterol, but increases blood levels of triglycerides and reduces high-density lipoprotein-cholesterol HDL-cholesterol.
Replacing total fat or saturated fats with carbohydrates is not associated with reduced risk of CVD. Additional research is needed to determine whether this relationship is consistent across categories of carbohydrates e. Therefore, saturated fats in the diet should be replaced with polyunsaturated and monounsaturated fats. As discussed in Chapter 2 , the main sources of saturated fats in the U.
Although some saturated fats are inherent in foods, others are added. Healthy eating patterns can accommodate nutrient-dense foods with small amounts of saturated fats, as long as calories from saturated fats do not exceed 10 percent per day, intake of total fats remains within the AMDR, and total calorie intake remains within limits.
When possible, foods high in saturated fats should be replaced with foods high in unsaturated fats, and other choices to reduce solid fats should be made see Chapter 2. Individuals should limit intake of trans fats to as low as possible by limiting foods that contain synthetic sources of trans fats, such as partially hydrogenated oils in margarines, and by limiting other solid fats.
A number of studies have observed an association between increased intake of trans fats and increased risk of CVD. This increased risk is due, in part, to its LDL-cholesterol-raising effect. Trans fats occur naturally in some foods and also are produced in a process called hydrogenation. Hydrogenation is used by food manufacturers to make products containing unsaturated fatty acids solid at room temperature i. Partial hydrogenation means that some, but not all, unsaturated fatty acids are converted to saturated fatty acids; some of the unsaturated fatty acids are changed from a cis to trans configuration.
Artificial trans fatty acids are found in the partially hydrogenated oils  used in some margarines, snack foods, and prepared desserts as a replacement for saturated fatty acids. Although food manufacturers and restaurants have reduced the amounts of artificial trans fats in many foods in recent years, these fats can still be found in some processed foods, such as some desserts, microwave popcorn, frozen pizza, margarines, and coffee creamers.
Natural trans fats are present in small quantities in dairy products and meats, and consuming fat-free or low-fat dairy products and lean meats and poultry will reduce the intake of natural trans fats from these foods. Because natural trans fats are present in dairy products and meats in only small quantities and these foods can be important sources of nutrients, these foods do not need to be eliminated from the diet.
The body uses cholesterol for physiological and structural functions but makes more than enough for these purposes. Therefore, people do not need to obtain cholesterol through foods. The Key Recommendation from the Dietary Guidelines to limit consumption of dietary cholesterol to mg per day is not included in the edition, but this change does not suggest that dietary cholesterol is no longer important to consider when building healthy eating patterns.
As recommended by the IOM,  individuals should eat as little dietary cholesterol as possible while consuming a healthy eating pattern.
In general, foods that are higher in dietary cholesterol, such as fatty meats and high-fat dairy products, are also higher in saturated fats. The USDA Food Patterns are limited in saturated fats, and because of the commonality of food sources of saturated fats and dietary cholesterol, the Patterns are also low in dietary cholesterol. For example, the Healthy U.
Current average intake of dietary cholesterol among those 1 year and older in the United States is approximately mg per day. Strong evidence from mostly prospective cohort studies but also randomized controlled trials has shown that eating patterns that include lower intake of dietary cholesterol are associated with reduced risk of CVD, and moderate evidence indicates that these eating patterns are associated with reduced risk of obesity.
More research is needed regarding the dose-response relationship between dietary cholesterol and blood cholesterol levels. Adequate evidence is not available for a quantitative limit for dietary cholesterol specific to the Dietary Guidelines. Examples of CDRH-regulated devices include cellular phones , airport baggage screening equipment , television receivers , microwave ovens , tanning booths , and laser products.
CDRH regulatory powers include the authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or noncompliant products.
CDRH also conducts limited amounts of direct product testing. Clearance requests are for medical devices that prove they are "substantially equivalent" to the predicate devices already on the market.
Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example it may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed. Cosmetic products are not, in general, subject to premarket approval by the FDA unless they make "structure or function claims" that make them into drugs see Cosmeceutical.
However, all color additives must be specifically FDA approved before manufacturers can include them in cosmetic products sold in the U. The FDA regulates cosmetics labeling, and cosmetics that have not been safety tested must bear a warning to that effect. Though the cosmetic industry is predominantly responsible in ensuring the safety of its products, the FDA also has the power to intervene when necessary to protect the public but in general does not require pre-market approval or testing.
Companies are required to place a warning note on their products if they have not been tested. Experts in cosmetic ingredient reviews also play a role in monitoring safety through influence on the use of ingredients, but also lack legal authority. Overall the organization has reviewed about 1, ingredients and has suggested that several hundred be restricted, but there is no standard or systemic method for reviewing chemicals for safety and a clear definition of what is meant by 'safety' so that all chemicals are tested on the same basis.
CVM's primary focus is on medications that are used in food animals and ensuring that they do not affect the human food supply. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers. In , Congress passed a law requiring color warnings on cigarette packages and on printed advertising, in addition to text warnings from the U.
The nine new graphic warning labels were announced by the FDA in June and were scheduled to be required to appear on packaging by September The implementation date is uncertain, due to ongoing proceedings in the case of R. Food and Drug Administration. Reynolds , Lorillard , Commonwealth Brands Inc.
A First Amendment lawyer, Floyd Abrams , is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny.
District Court for the District of Columbia temporarily halted the new labels, likely delaying the requirement that tobacco companies display the labels.
Supreme Court ultimately could decide the matter. In July , the FDA announced a plan that would reduce the current levels of nicotine permitted in tobacco cigarettes. Ronald Sherman permission to produce and market medical maggots for use in humans or other animals as a prescription medical device. Medical maggots represent the first living organism allowed by the Food and Drug Administration for production and marketing as a prescription medical device.
In June , the FDA cleared Hirudo medicinalis medicinal leeches as the second living organism to be used as a medical device. The FDA also requires milk to be pasteurized to remove bacteria. In addition to its regulatory functions, the FDA carries out research and development activities to develop technology and standards that support its regulatory role, with the objective of resolving scientific and technical challenges before they become impediments.
The FDA's research efforts include the areas of biologics, medical devices, drugs, women's health, toxicology, food safety and applied nutrition, and veterinary medicine. The FDA has collected a large amount of data through decades.
Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals, with one exception being the short-lived Vaccine Act of The history of the FDA can be traced to the latter part of the 19th century and the U. Under Harvey Washington Wiley , appointed chief chemist in , the Division began conducting research into the adulteration and misbranding of food and drugs on the American market.
Wiley's advocacy came at a time when the public had become aroused to hazards in the marketplace by muckraking journalists like Upton Sinclair , and became part of a general trend for increased federal regulations in matters pertinent to public safety during the Progressive Era. The serum was originally collected from a horse named Jim , who had contracted tetanus. The act applied similar penalties to the interstate marketing of "adulterated" drugs, in which the "standard of strength, quality, or purity" of the active ingredient was not either stated clearly on the label or listed in the United States Pharmacopoeia or the National Formulary.
The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry.
By the s, muckraking journalists, consumer protection organizations, and federal regulators began mounting a campaign for stronger regulatory authority by publicizing a list of injurious products that had been ruled permissible under the law, including radioactive beverages , the mascara Lash lure, which caused blindness, and worthless "cures" for diabetes and tuberculosis. The resulting proposed law was unable to get through the Congress of the United States for five years, but was rapidly enacted into law following the public outcry over the Elixir Sulfanilamide tragedy, in which over people died after using a drug formulated with a toxic, untested solvent.
The new law significantly increased federal regulatory authority over drugs by mandating a pre-market review of the safety of all new drugs, as well as banning false therapeutic claims in drug labeling without requiring that the FDA prove fraudulent intent.
Soon after passage of the Act, the FDA began to designate certain drugs as safe for use only under the supervision of a medical professional, and the category of " prescription-only " drugs was securely codified into law by the Durham-Humphrey Amendment.
These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs. This marked the start of the FDA approval process in its modern form. These reforms had the effect of increasing the time, and the difficulty, required to bring a drug to market. The act extended the patent exclusivity terms of new drugs, and tied those extensions, in part, to the length of the FDA approval process for each individual drug.
For generic manufacturers, the Act created a new approval mechanism, the Abbreviated New Drug Application ANDA , in which the generic drug manufacturer need only demonstrate that their generic formulation has the same active ingredient, route of administration, dosage form, strength, and pharmacokinetic properties "bioequivalence" as the corresponding brand-name drug.
This act has been credited with in essence creating the modern generic drug industry. Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In two instances, state governments have sought to legalize drugs that the FDA has not approved.
Under the theory that federal law passed pursuant to Constitutional authority overrules conflicting state laws, federal authorities still claim the authority to seize, arrest, and prosecute for possession and sales of these substances, [ citation needed ] even in states where they are legal under state law.
The first wave was the legalization by 27 states of laetrile in the late s. This drug was used as a treatment for cancer, but scientific studies both before and after this legislative trend found it to be ineffective. Though Virginia passed a law with limited effect in , a more widespread trend began in California in The Critical Path Initiative  is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.
Randall in , creating a program for medical marijuana. A court case, Abigail Alliance v. The Abigail Alliance argued that the FDA must license drugs for use by terminally ill patients with "desperate diagnoses," after they have completed Phase I testing. The US Supreme Court declined to hear the case, and the final decision denied the existence of a right to unapproved medications. Critics of the FDA's regulatory power argue that the FDA takes too long to approve drugs that might ease pain and human suffering faster if brought to market sooner.
The AIDS crisis created some political efforts to streamline the approval process. However, these limited reforms were targeted for AIDS drugs, not for the broader market. This has led to the call for more robust and enduring reforms that would allow patients, under the care of their doctors, access to drugs that have passed the first round of clinical trials. The widely publicized recall of Vioxx , a non-steroidal anti-inflammatory drug now estimated to have contributed to fatal heart attacks in thousands of Americans, played a strong role in driving a new wave of safety reforms at both the FDA rulemaking and statutory levels.
However, a number of pre- and post-marketing studies suggested that Vioxx might increase the risk of myocardial infarction, and this was conclusively demonstrated by results from the APPROVe trial in Faced with numerous lawsuits, the manufacturer voluntarily withdrew it from the market.
The example of Vioxx has been prominent in an ongoing debate over whether new drugs should be evaluated on the basis of their absolute safety, or their safety relative to existing treatments for a given condition. In the wake of the Vioxx recall, there were widespread calls by major newspapers, medical journals, consumer advocacy organizations, lawmakers, and FDA officials  for reforms in the FDA's procedures for pre- and post- market drug safety regulation.
In , a congressionally requested committee was appointed by the Institute of Medicine to review pharmaceutical safety regulation in the U.
The committee was composed of 16 experts, including leaders in clinical medicinemedical research, economics, biostatistics , law, public policy, public health, and the allied health professions, as well as current and former executives from the pharmaceutical , hospital, and health insurance industries. The authors found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.
As of , Risk Minimization Action Plans RiskMAPS have been created to ensure risks of a drug never outweigh the benefits of that drug within the postmarketing period. This program requires that manufacturers design and implement periodic assessments of their programs' effectiveness. The Risk Minimization Action Plans are set in place depending on the overall level of risk a prescription drug is likely to pose to the public.
This became a major concern of pediatricians as evidence accumulated that the physiological response of children to many drugs differed significantly from those drugs' effects on adults. Children react different to the drugs because of many reason, including size, weight, etc.
There were several reasons that not many medical trials were done with children. For many drugs, children represented such a small proportion of the potential market, that drug manufacturers did not see such testing as cost-effective. Also, because children were thought to be ethically restricted in their ability to give informed consent , there were increased governmental and institutional hurdles to approval of these clinical trials, as well as greater concerns about legal liability. Thus, for decades, most medicines prescribed to children in the U.
An initial attempt by the FDA to address this issue was the FDA Final Rule on Pediatric Labeling and Extrapolation, which allowed manufacturers to add pediatric labeling information, but required drugs that had not been tested for pediatric safety and efficacy to bear a disclaimer to that effect. However, this rule failed to motivate many drug companies to conduct additional pediatric drug trials. However, this new rule was successfully preempted in federal court as exceeding the FDA's statutory authority.
While this debate was unfolding, Congress used the Food and Drug Administration Modernization Act to pass incentives that gave pharmaceutical manufacturers a six-month patent term extension on new drugs submitted with pediatric trial data. In the Pediatric Research Equity Act of , Congress codified the FDA's authority to mandate manufacturer-sponsored pediatric drug trials for certain drugs as a "last resort" if incentives and publicly funded mechanisms proved inadequate.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Medication errors have been reported in which other insulin products, particularly rapid-acting insulins, have been accidentally administered instead of an insulin glargine product.
To avoid medication errors between insulin glargine products and other insulin products, patients should be instructed to always verify the insulin label before each injection. Table 6 includes clinically significant drug interactions with Basaglar.
All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control.
It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery.
Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Basaglar. There are no well-controlled clinical studies of the use of insulin glargine in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Subcutaneous reproduction and teratology studies have been performed with another insulin glargine product and with regular human insulin in rats and Himalayan rabbits. This other insulin glargine product was given to female rats before mating, during mating, and throughout pregnancy at dose up to 0.
In rabbits, doses of 0. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats and rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal. Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk.
Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when Basaglar is administered to a nursing woman. Use of Basaglar is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses. The safety and effectiveness of Basaglar in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established.
The dosage recommendation when changing to Basaglar in pediatric patients age 6 to 15 years with type 1 diabetes is the same as that described for adults [see Dosage and Administration 2. As in adults, the dosage of Basaglar must be individualized in pediatric patients age 6 to 15 years with type 1 diabetes based on metabolic needs and frequent monitoring of blood glucose.
In the pediatric clinical trial, pediatric patients age 6 to 15 years with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions 6. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Nevertheless, caution should be exercised when Basaglar is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions.
Hypoglycemia may be difficult to recognize in the elderly. The effect of renal impairment on the pharmacokinetics of Basaglar has not been studied.
Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with renal impairment [see Warnings and Precautions 5. The effect of hepatic impairment on the pharmacokinetics of Basaglar has not been studied.
However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with hepatic impairment [see Warnings and Precautions 5. Excess insulin administration relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions 5. Mild episodes of hypoglycemia can be treated with oral glucose.
Adjustments in drug dosage, meal patterns, or physical activity level may be needed. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately. Basaglar insulin glargine injection is a long-acting insulin for subcutaneous use.
Insulin glargine is a recombinant human insulin analog [see Clinical Pharmacology 12 ]. Basaglar is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli K12 as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain.
Insulin glargine has the following structural formula:. Basaglar is a clear, colorless, sterile aqueous solution of insulin glargine. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. Basaglar has a pH of approximately 4. The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism.
Insulin and its analog lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis. The pharmacodynamic profile for Basaglar was determined after subcutaneous administration of a single 0. The median time to maximum effect of Basaglar measured by the peak rate of glucose infusion was approximately The pharmacodynamic profile of Basaglar following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak.
A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0. After subcutaneous injection of 0. The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual. The pharmacokinetic profile for Basaglar was determined after subcutaneous administration of a single 0. The median time to maximum serum insulin concentration was 12 hours after injection.
On average, serum insulin concentrations declined to baseline by approximately 24 hours. The in vitro activity of M1 and M2 were similar to that of insulin. Age, Race, and Gender: Effect of age, race, and gender on the pharmacokinetics of Basaglar has not been evaluated. Effect of BMI on the pharmacokinetics of Basaglar has not been evaluated. In mice and rats, standard two-year carcinogenicity studies with another insulin glargine product were performed at doses up to 0.
The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats statistically significant and male mice not statistically significant in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown. Another insulin glargine product was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells Ames- and HGPRT-test and in tests for detection of chromosomal aberrations cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters.
In a combined fertility and prenatal and postnatal study of another insulin glargine product in male and female rats at subcutaneous doses up to 0. Consequently, a reduction of the rearing rate occurred in the high-dose group only.
Similar effects were observed with NPH insulin. In general, the reduction in glycated hemoglobin HbA 1c with this other insulin glargine product was similar to that with NPH insulin. Randomized were adults with type 1 diabetes. Mean age was The mean BMI was approximately Observed HbA 1c data at 24 weeks were available from Regular human insulin was administered before each meal.
This other insulin glargine product was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily.
In Study A, the average age was The mean duration of diabetes was In Study B, the average age was The majority of patients were Caucasian Insulin lispro was used before each meal. This other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was Type 1 Diabetes — Pediatric see Table 9. Patients were randomized to either this other insulin glargine product administered once daily at bedtime or NPH insulin administered once or twice daily.
The mean duration of diabetes was 4. Similar effects on HbA 1c see Table 9 were observed in both treatment groups. A total of patients were randomized. Three patients randomized to Basaglar did not receive study drug and were not included in efficacy analysis. The average age was approximately 59 years.
This other insulin glargine product administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA 1c and fasting glucose see Table The rate of hypoglycemia was similar in this other insulin glargine product and NPH insulin treated patients [see Adverse Reactions 6.
Regular human insulin was used before meals, as needed. This other insulin glargine product had similar effectiveness as either once- or twice daily NPH insulin in reducing HbA 1c and fasting glucose see Table 11 with a similar incidence of hypoglycemia [see Adverse Reactions 6.
The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the ETDRS scale. HbA 1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data.
After this other insulin glargine product or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. This other insulin glargine product group had a smaller mean reduction from baseline in HbA 1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in this other insulin glargine product group see Table Both treatment groups had a similar incidence of reported symptomatic hypoglycemia.
Patients were also treated with insulin lispro at mealtime. This other insulin glargine product administered at different times of the day resulted in similar reductions in HbA 1c compared to that with bedtime administration see Table In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to injection of this other insulin glargine product regardless of time of administration.
No patients in the other two arms discontinued for this reason. This other insulin glargine product given before breakfast was at least as effective in lowering HbA 1c as this other insulin glargine product given at bedtime or NPH insulin given at bedtime see Table Five-year Trial Evaluating the Progression of Retinopathy. The numbers of retinal adverse events reported for this other insulin glargine product and NPH insulin treatment groups were similar for patients with type 1 and type 2 diabetes.
Mean baseline HbA 1c was 8. Patients with pre-specified post-baseline eye procedures pan-retinal photocoagulation for proliferative or severe nonproliferative diabetic retinopathy, local photocoagulation for new vessels, and vitrectomy for diabetic retinopathy were also considered as 3-step progressions regardless of actual change in ETDRS score from baseline.
Retinopathy graders were blinded to treatment group assignment. The results for the primary endpoint are shown in Table 13 for both the per-protocol and Intent-to-Treat populations, and indicate similarity of this other insulin glargine product to NPH in the progression of diabetic retinopathy as assessed by this outcome.
The objective of the trial was to demonstrate that use of this other insulin glargine product could significantly lower the risk of major cardiovascular outcomes compared to standard care. The first co-primary endpoint was the time to first occurrence of a major adverse cardiovascular event defined as the composite of CV death, nonfatal myocardial infarction and nonfatal stroke.