3-D printing of Pharmaceuticals by Jaikumar Pareta

 Developed at the Massachusetts Institute of Technology (MIT), computer-aided 3D-printing technology has opened up exciting and revolutionary new possibilities in customized medicines.

 

Aprecia successfully deployed the technology and developed the world’s first 3D-printed Spritam (chemical name: Levetiracetam), a drug to treat seizures in epileptic patients. Produced by sandwiching a powdered form of the drug between liquid materials and bonding them at a microscopic level, these printed pills are superbly porous and dissolve rapidly on contact with liquids. It’s an unparalleled feature for sure, and one that makes it remarkably effective in its core purpose — countering sudden seizures.

3D printing has enabled the creation of high-dose rapid-dissipation pills, affording doctors reliable customization and complete control over the speed and strength of delivered dosage.

By simply altering a pill’s surface area through the printing of complex shapes, one can control not only the strength of a released dose but also the time over which it’s released. This goes a long way toward making administered dosage safer and far more effective.

Manufacturers can also modify their products according to individual preferences, with customized dose strength, pill size, flavors, and colors to choose from. Assuming easy availability of pharmaceutical compounds in powder form, patients can ditch unwieldy tablets, capsules, or liquids in favor of medicines that are far easier to consume. Customizability is especially useful when preparing doses for patients who find swallowing difficult, such as young children or the physically impaired.

3D printing represents a significant breakthrough in an era of customized medicine and tailored treatments.

This breakthrough technology could also allow manufacturers to shift their production and distribution processes closer to consumers. With constant improvements in design and operational efficiency, printers of varying sizes and capacities could be deployed at bespoke locations that are convenient for patients. Hospitals and pharmacies could manufacture prescriptions on their own premises, eliminating the need to stock vast quantities of generics. They would also be able to produce specialized or uncommon compounds in-house, saving patients a considerable wait, and perhaps saving more lives in time-sensitive critical situations. With such flexibility and scalability afforded to supply chains, both suppliers and consumers can benefit from the low costs and prices that operational efficiencies bring.

Some speculate 3D printing will become so commonplace that patients could even print their own drugs at home.

The technology could, in theory, allow users to print drugs of any size, shape, and dosage with ease. All they’d need is a downloadable recipe, basically a set of instructions that the printer reads and follows. As long as their home printer is stocked with the necessary base compounds, they could synthesize any and every formulation they’d need. It’d be just like using recipes from a cookbook, only it’d take only half as much work:

To make a batch of cookies you’ve never made before:

1. Find the recipe you want
2. Download a copy
3. Print
4. Follow the recipe
5. Bake
6. Clean up after yourself

To make a batch of pharmaceutical prescriptions you’ve never made before:

1. Find the recipe you want
2. Download a copy
3. Print

When it’s easier to make a batch of pills than it is to bake cookies, it ought to make you wonder.

While there’s little scope for tampering in current pharmaceutical manufacturing processes, there’s some concern about its likelihood when implementing 3D printing methodologies. There’s also the possibility of hacked machines producing counterfeit medications or being used to mask illegal drugs as legitimate medication.

The wide reach and global nature of such technologies also means the lines for liabilities are blurry.

Drug companies would need to ensure that their products’ recipes and regulatory norms are adhered to. They’d have to ensure foolproof print processes that are safeguarded against human error as well as sabotage. They would also need to ensure their devices are well secured in case unscrupulous entities try to reverse-engineer proprietary products. Drug regulatory authorities would also have to establish unprecedented guidelines for the approval of mass-marketed 3D-printed drug products.

More importantly, in case of technical errors or malfunctions that result in incorrectly printed dosages that cause harm to or the demise of a patient, who is to blame?

Does the onus fall on the drug company that created the recipe, on the patient who printed the recipe, or on an intermediary that manufactures doses or maintains the machines?

While there are several significant concerns that need addressing before 3D pharmaceutical printing technology goes mainstream, the benefits are well worth the bother.

This technology stands to revolutionize the pharmaceutical manufacturing industry, with possibilities that sound straight out of science fiction. Pills created to release a cocktail of drugs over definite intervals could wrap up a whole day’s worth of dosage into a single, easy-to-swallow pill. Tell grandpa to toss out that old pill organizer; he’ll get everything he needs from a single tab, no fuss or chance to forget. Imagine the possibilities for specialized pills that treat niche ailments, which can be developed and produced at a fraction of current costs, all tailored to your prescription and individual preferences.

making it cheaper because the whole process of testing drugs would become more efficient. While the home 3D printing of drugs may not be possible any time soon, it might be possible to 3D print sample tissues and organs for drug testing purposes. Imagine testing out drugs on 3D human organs instead of on animals or synthetic models. And 3D printing might allow for new types of compounds and medications, based on new geometries and configurations made possible with 3D printing.

Of course, the big wildcard in all this is the approval process of the FDA. Yes, this is the same FDA that sometimes gets blamed for the long process of bringing new drugs to market quickly and efficiently. Add in the “gee whiz” aspect of 3D printing, and it’s easy to see potential regulatory nightmares facing other FDA approvals.

We may never do away with the need for the corner pharmacy to fill prescriptions – but 3D printers could fundamentally change the way patients take certain types of medicine. 3D printers could make possible a world of bespoke medicine in which patients play an active role in bringing their own custom-designed pills to market.

Modern Chip Technology in Life Sciences by Jaikumar Pareta

The healthcare arena is on a clear path towards preventative and personalized medicine.  Measurements of health status are essential in advising patients and healthcare professionals on the most appropriate preventive or curative measures. However, our ability to measure our health status is hampered by the complexity of instrumentation required to acquire that data, and by the complexity of the analysis required to turn that data into actionable information.

But, semiconductor technologies have excelled at making extremely complex instrumentation and data analytics available to consumers at the lowest possible cost. I believe we can tune semiconductor technology such that we can benefit from its power in enabling health measurements anywhere, anytime, by anyone, and at very low cost.

Just look at the Apple A9 chip used in the latest iPhones: It contains more than three billion transistors. That’s pretty impressive on its own — but when you look at its price of around $22 U.S. dollars, it becomes even more remarkable. For decades now, the chip industry has succeeded in offering more and more functionality at increasingly low prices. It is our aim to bring the enormous power of silicon-based chip technology to the life sciences, too.

First and foremost, silicon-based chip technology makes medical instruments smaller and less expensive. In doing so, it makes such devices more accessible to consumers. A good example of this is our project in which we integrate an entire medical laboratory onto a chip measuring just a few square centimeters (cm²). The chip will be capable of analyzing the molecules or cells contained in body fluids (DNA, proteins, viruses, blood cells, etc.) autonomously. This will make it possible to carry out sophisticated tests quickly in places where it was previously impossible: In the hospital ward, at a doctor’s practice, and even in the patient’s home. Continued development of this technology could lead to mainstream, inexpensive DNA tests.

A second reason to bring chip technology to the life sciences is to increase the speed or throughput of medical instruments. Imagine if you were able to read, or sequence, DNA using a chip. It would then become possible to integrate a large number of these sequencing components onto a small area, enabling high-throughput DNA sequencers.

Another great example of chip technology bringing smaller and faster instruments to the life science arena is a new prototype chip called a cell sorter. It’s a device of only 4x2 cm that can analyze a milliliter of blood (e.g. searching for circulating tumor cells). The blood sample flows through a microfluidic channel and, one by one, cells pass over an imager while being illuminated by a laser. Then, based on the holographic image on the sensor, a powerful computation chip reconstructs an image of each individual cell, thanks to lens-free microscopy technology.

The cell is then identified (e.g., as a tumor cell or a white blood cell) and if it is a type that needs to be investigated, it is separated in a distinct microfluidic channel. This is done with the help of steam bubbles generated by miniaturized heating elements in the different output channels, where the live cells are collected for further examination. Such a high-throughput cell sorter chip could be used by medical doctors to do complicated tests on the fly, such as screening blood cells in a patient’s blood sample.

Think of a cancer specialist, who would immediately be able to see if a patient has tumor cells within their blood, or is able to determine if a chemotherapy patient’s treatment should be continued or modified after checking the blood for remaining tumor cells. The cell sorter chip also makes it possible to see if a patient’s blood is contaminated by specific bacteria, allowing doctors to start a targeted treatment immediately.

Chip technology is also of interest for cytometric devices (counting and examining cells), either because the devices themselves can be made smaller and more compact, or because their throughput is enhanced. Counting and examining cells may be of value, for instance, in following up leukemia treatment: A disposable chip can be used to quickly count the number of blood cells so that the doctor can tell the patient — on the spot — whether the treatment is working.

‘Cell sorter' chip that identifies and sorts 3,000 cells per second.

Another application is cell therapy in which human cells are used as medicine. One risk with this treatment is that wrongly programmed cells might be injected inadvertently, which could lead to tumor formation. Cytometric devices are needed to check all of the to-be-injected cells before they are administered to the patient. Thanks to chip technology, this can be done faster, better, and at lesser cost.

Following the famous Moore’s Law, chip technology evolves at a very fast pace. The focus is on developing ever smaller building blocks for the chips, making them faster and more energy efficient. Today’s most advanced chips are made in 20 nanometer (nm) and 14 nm technologies. For the life science applications mentioned above, research centers such as imec are using much ‘older’ technologies, namely 180 nm and 130 nm technology.

This year, imec will go a step further and test more scaled chip technologies. At present, no one knows what these more advanced chip technologies might mean for medical instruments. After all, if the ‘old’ technologies already mean such a revolution for equipment manufacturers, doctors, and patients, it will be exciting to see what the newer technologies will bring to detection and treatment.

Protein and Muscle Strength:Maintaining your muscle mass by jaikumar pareta

We are constantly besieged by media reports about how overweight we are as a population and the detrimental effects that this has on our health. However, little spotlight, if any, is shed on the importance of maintaining muscle mass as we age. More often than not, concern regarding muscle is overshadowed by the “battle of the bulge” narrative that we have become so familiar with. Muscle mass and strength decrease naturally with age and by the age of 40, an average person will lose their muscle mass at a rate of roughly 1% annually. This sounds like a relatively small amount, but by the age of 70, cumulatively, this could mean the loss of up to one third of the body’s muscle mass.

But losing weight is good, right?

No, not necessarily. A loss of body weight due to a loss of muscle can have serious adverse effects. Muscle is vital for strength, function and mobility, and it also serves as the epicentre for many of the body’s cellular processes. In other words, the more muscle you have, the more capacity your body has for processing nutrients and maintaining important processes.

Muscle, like bone, is in a constant state of remodelling, or “turnover”, the simultaneous processes of protein production and breakdown. Although there are several factors that cause the loss of muscle with ageing, it is ultimately rooted in an imbalance in protein production and breakdown in the body. Muscle breakdown can occur at a modest rate, thus, even a slight disturbance in this production-breakdown cycle can result in meaningful differences in remaining stores. Over time this could contribute to the loss of large volumes of muscle.

Sarcopenia

As we age, insufficient calorie and protein intake from the diet can lead to a more rapid, unintentional loss of body weight and muscle. This loss of muscle is called sarcopenia. Pronounced ‘sar-co-pee-nee-a,’ a Greek term meaning “poverty of the flesh,” this condition is the age-related progressive loss of muscle mass, function, quality, and strength. Sarcopenia can contribute to mobility issues, osteoporosis, frailty, falls and fractures, decreased physical activity levels and can threaten independent living. Despite this, little is known about how prevalent sarcopenia is globally, but research suggests it may occur in up to 33% of people over 50 living in the community, with higher prevalence in long-term and acute care settings (Cruz-Jentoft et al, 2014). Some have suggested that this may increase to more than half of those aged over 80 years (Baumgartner et al, 1998).

Sarcopenia can very quickly affect our physical capabilities and quality of life: in real terms, it can lead to frailty and increase the risk of falls and fractures in older adults. Worryingly, when coupled with other common conditions associated with ageing, the effects of sarcopenia can be even more pronounced. For example, in those with osteoporosis, sarcopenia dramatically increases the existing risk of injurious falls and fractures. Therefore, preventing sarcopenia can, in turn, lessen the potential burden on other health issues that are commonly associated with ageing.

How can I avoid sarcopenia?

You can’t avoid the loss of muscle mass altogether as it is a natural component of the ageing process. However, with regular resistance exercise or ‘strength training’ and appropriate dietary considerations, you can help to ward-off or slow the progression of sarcopenia.

1. Start strength training

Strength training is essential. It can slow down the natural loss of muscle that comes with ageing, build strength in muscles and connective tissues, and improve flexibility and coordination. Encouragingly, strength training can be done anywhere: at home, in the garden, at a park or at a gym facility and should be carried out a minimum of three times per week to have a beneficial effect on muscle mass and strength. The three major regions of the body involved with strength include the trunk and back, the upper body and the lower body.

It is more effective to prevent or slow the progression of sarcopenia, than it is to treat the existing condition. Strength training programmes for those with sarcopenia can successfully improve functionality, but the reversal of the condition once established, can be very difficult. Strength training in older adults is often less effective than in their younger counterparts partly because they, particularly older women, are often already too weak to perform the intensity of exercise required to build muscle. Therefore, the best strategy is to start your strength training as earlier as possible. In in other words, use it or lose it. Incorporating a strength training programme into your routine can offset the potentially harmful effects of loss of muscle mass in old age. That being said, it is never too late to get started. Research has shown that a programme of progressive strength training can increase protein production rates in older adults in as little as two weeks 

Strength training can have a significant effect on your overall health too, reducing blood pressure, improving cholesterol levels and reducing risk of diabetes. In addition, the “everyday” benefits are obvious too, such as increased ability for lifting or moving objects at home, gardening and playing with children (or grandchildren), as strength, co-ordination and flexibility improve. Click on the final link in the resources section (below) for additional information on strength training, including activities to help you build strength, maintain bone density, improve balance, and test coordination.

2. Eat more quality protein

In addition to beginning a strength training programme, the foods we consume play an essential role in maintaining muscle and slowing the development of sarcopenia. Several nutrients have been identified as beneficial to the maintenance of muscle mass, including protein, vitamin D, vitamin B12 and folic acid, among others. However, it is the protein in particular, that proves crucial to muscle maintenance as we age.

On a cellular level, protein instructs the body to build muscle and to provide the necessary building blocks (amino acids) for this new muscle tissue. With age, there is a gradual decrease in sensitivity to the signal that initiates this process, therefore older adults need to increase protein intake from food to offset the decrease in its uptake. When accompanied by an increased protein intake, the effect of strength training on muscle production is significantly increased.

The ideal amount of protein intake necessary to prevent or slow down the progression of sarcopenia has yet to be determined. However, some suggest that intakes need to be higher than the present recommendation (0.8g protein per kg body weight, per day) to see improvements in older adults. Therefore, it is suggested that older adults should aim to consume between 1.0–1.2g protein per kg body weight, per day)(Dreyer & Volpi, 2005). The timing of meals or snacks can play an important role also. Immediately after training, muscle is more sensitive to the effects of the protein, therefore eating shortly after training can make improve protein uptake by the body.

Adding some extra protein to everyday foods, as part of a healthy balanced diet, can be simple to do. 

Warning: Increasing protein intake is not advisable for people with renal dysfunction, kidney disease and those taking certain medications. Always consult your General Practitioner before altering your diet.

Warning: Before commencing a new exercise routine, always consult your General Practitioner or a Chartered Physiotherapist to guide you with an age- and intensity- appropriate strength training programme.

10 tips for adding extra protein to your diet Protein is the building block from which muscle is made and is essential for both growth and repair. To stay fit and strong eat a variety of protein-rich foods each day. Great sources include lean meat, poultry and fish. Oily fish like salmon, sardines and kippers are packed with protein and heart-healthy omega-3 fats, and should be eaten twice a week. Milk, yoghurt and cheese are also excellent sources of protein and are rich in calcium too. Eating beans, eggs and nuts is a simple way of boosting protein in your diet. Here are some simple ideas for boosting the protein content of some everyday meals and snacks: 1. Add hard-boiled eggs to salads. 2. Add tinned tuna or tinned salmon to salads or pasta dishes. 3. Eat Greek or low-calorie unsweetened yoghurt alone as a snack or add to fruit and cereal, at breakfast. 4. Add milk or yoghurt to a fruit smoothie. 5. Add nut butter to sandwiches, toast, crackers, or muffins, or use as a dip for vegetables and fruit. 6. Add skimmed milk powder to cream soups, mashed potatoes, casseroles, puddings, and milk-based desserts. 7. Add skimmed milk powder to regular milk for use in drinks, hot porridge, breakfast cereals, custard and milk puddings. 8. Add nuts, seeds, or wheat germ to casseroles, breads, muffins and pancakes, or use nuts, seeds, or wheat germ to top fruit, cereal, ice cream, and yogurt or in place of breadcrumbs. 9. Add high quality vegetable protein sources like soy, quinoa and pulses (e.g., chickpeas, kidney beans, butter beans and lentils) to soups, casseroles, or salads. 10. Add cheese to sauces, vegetables, salads, mashed potatoes, scrambled eggs and omelettes and casseroles

Strategies for talking to health care professionals by Jaikumar pareta

In the past, general doctors’ practices were single handed, or had two or three like-minded doctors working as a group. These doctors were usually male, worked full-time, frequently made house calls, and knew their patients well.

The local doctor was respected and usually lived within the local community and their knowledge extended across generations because they knew their patients and their patients’ families for years. Emphasis was largely on diagnosis, treatment and reassurance, based on the practitioner’s previous observations and experiences, and patients seldom questioned the advice or treatment offered.

Modern family practice is now multidisciplinary, composed of a group of family doctors, physiotherapists, occupational therapists, counsellors and nurse specialists working from purpose-built premises such as health centres with greater gender balance. While General Practitioners (GPs) today have undergone many years of structured training, and are committed to lifelong learning, they may not know their patient’s family history, living situations or other key determinants of health. Many physicians may work part-time or live outside the local community.

Work practices and the sheer volume of business have resulted in time constraints, limiting normal consultation times to an average of ten minutes per patient. Continuity is not as dependent on building long-term relationships; instead, doctors rely on computerised records. Diagnosis and advice is now evidence-based and subject to protocols.

Emphasis has switched towards early intervention, accurate diagnosis, targeted screening and wellness programs, all leading to increased life expectancy and, most importantly, quality-adjusted life years.

For those of us who benefited from the previous system, we need to develop new strategies for negotiating the best result from a ten-minute consultation with someone we are less familiar with.

How can you best maximise a ten-minute doctor consultation?

Before the consultation

• Consider seeking annual routine screening after the age of 65. This is useful to establish a baseline for routine blood tests, blood pressure and other vital signs while we are well. This can often be arranged through the practice nurse and may be combined with driving licence examinations, key milestones in your life (such as a birthday) or when receiving annual flu vaccinations.
• You may wish to be accompanied by a relative or friend, particularly if you are stressed over something. If so, negotiate their role prior to attendance: to listen and confirm what is said, to support you with their observations, as an advocate, or to assist with decision-making. Explain this person’s role and relationship to the GP so that it is clear to all.
• Prior to a GP consultation, list your main concern, secondary issues, and physical signs such as signs of disease that you can see, feel, hear or measure, such as swellings, temperatures, pulse rate, paleness, or skin changes. Symptoms are changes only you can describe such as pain, palpitations, nausea, and breathlessness on exertion. Also, describe any treatments you have tried beforehand. Try to restrict this to a few minutes, leaving more time for the cursory examination and detailed questions. If your medical record is more extensive, bring notes which the GP can review. Go suitably dressed and prepare to be examined, with access to appropriate areas, to save time.
• Arrive fifteen minutes early and check in as there may be a late cancellation. However, be prepared to wait patiently. Delayed appointments often signify a popular and empathetic practitioner, so bring a book.

During the consultation

• After brief introductions, be direct about what is bothering you.
• State your concerns, any secondary concerns, symptoms, signs and previous treatment. This allows the doctor to carry out a cursory examination, check pulse, blood pressure, heart sounds, or chest sounds, touch the abdomen and glands, or examine a specific area such as a joint.
• The remaining time can be devoted to more detailed questions about what the GP is observing in order to arrive at a differential diagnosis.
• At this stage, the GP will suggest a plan of action, offer reassurance, recommend a prescription, require more tests, refer you to a specialist, or provide the schedule for follow-up. Don’t hesitate in taking notes, so that you can refer to these later.
• If you don’t understand terms, ask so that they can they be explained in simple language.

After the consultation

• Check out with reception. Be clear about next steps and follow up procedures.
• Consider “debriefing“ with the friend or close relative who has accompanied you to ensure you are all on the same page and clear about the course of treatment.
• Consider writing an “aide memoire“ or create a health diary which you can bring with you to future appointments.

In the words of Sir William Osler, one of the four founders of the Mayo Clinic, remember:

“Medicine is a science of uncertainty and an art of probability. A good physician treats the disease; the great physician treats the patient with the disease.”

• How has medical care changed for you over the years?
• What strategies do you use to improve your relationship with your doctor?
• What tips can you offer others for managing their health?

 

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Glossary

General Practitioners: General Practitioners/family doctors are specialist physicians trained in the principles of the discipline. They are personal doctors, primarily responsible for the provision of comprehensive and continuing care to every individual seeking medical care irrespective of age, sex and illness. 

Drug Trials Snapshot: RYZODEG, Review by Jaikumar pareta

What is the drug for?

RYZODEG is a mixture of a long-acting insulin and fast-acting insulin that improves blood sugar control in adults with diabetes mellitus (DM). It can be used in patients with type 1 or type 2 DM.

How is this drug used?

RYZODEG is available as a liquid that comes in a prefilled pen. It is injected once daily under the skin (subcutaneously).

What are the benefits of this drug?

In patients with type 1 and type 2 who need better blood sugar control, treatment with RYZODEG can lower HbA1c (hemoglobin A1c, which is a measure of blood sugar control). RYZODEG’s ability to lower HbA1c is in line with other, previously approved long-acting or pre-mixed (combination of long-acting and fast-acting) insulin products on the market.

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Subgroup analyses were conducted for sex, race and age.

• Sex:  RYZODEG worked similarly in men and women.
• Race:  In patients with type 1 DM, RYZODEG worked similarly in Whites and Black or African Americans.  There were too few Asian patients with type 1 DM to determine whether they responded differently to RYZODEG. In patients with type 2 DM, RYZODEG worked similarly among all racial groups studied.
• Age: RYZODEG worked similarly in patients below and above 65 years of age.

What are the possible side effects?

The most common side effects were low blood sugar (hypoglycemia), allergic reactions, injection site reactions, pitting at the injection site (lipodystrophy), itching, rash, swelling, and weight gain.

Were there any differences in side effects among sex, race and age?

Subgroup analyses were conducted for sex, race and age.

• Sex:  The risk of side effects was similar in men and women.
• Race:  In patients with type 1 DM, the majority of patients were white. Differences in side effects among races could not be determined. In patients with type 2 DM, the majority of patients were white and Asian. The risk of side effects was similar in Whites and Asians. Differences in side effects among other races could not be determined.
• Age: The risk of side effects was similar in patients below and above 65 years of age.

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved RYZODEG based on evidence from 1 clinical trial of 548 patients with type 1 DM and 4 clinical trials in 1860 patients (total) with type 2 DM.

Figure 1 summarizes how many men and women were enrolled in the clinical trials used to evaluate efficacy. Figure 1 includes the trials of patients with type 1 DM, and Figure 2 includes the trials of patients with type 2 DM.

Figure 1. Patients with Type 1 DM by Sex (Total Patients=548)

 Clinical Trial Data

Figure 2. Patients with Type 2 DM by Sex (Total Patients=1860)

Clinical Trial Data

The figures below summarize how many patients by racial group participated in the clinical trials used to evaluate efficacy. Figure 3 includes the trials of patients with type 1 DM, and Figure 4 includes the trials of patients with type 2 DM.

Figure 3. Patients with Type 1 DM by Racial Group

Clinical Trial Data

Table 1. Demographics of Efficacy Trials by Race-Patients with Type 1 DM

Race	Number of Patients	Percentage
White	495	90%
Black or African American	16	3%
Asian	7	1%
Other	30	5%

Figure 4. Patients with Type 2 DM by Racial Group

Clinical Trial Data

Table 2. Demographics of Efficacy Trials by Race—Patients with Type 2 DM

Race	Number of Patients	Percentage
White	878	47%
Black or African American	72	4%
Asian	900	48%
Other	10	1%

Clinical Trial Data

The figures below summarize how many patients by age group (at the start of the trials) participated in the clinical trials for type 1 patients (Figure 5) and type 2 patients (Figure 6).

Figure 5. Trials of Patients with Type 1 DM by Age Group

Clinical Trial Data

Figure 6. Trials of Patients with Type 2 DM by Age Group

Clinical Trial Data

How were the trials designed?

The benefits and side effects of RYZODEG 70/30 administered once-daily with the main meal of the day in patients with type 1 diabetes was evaluated in one randomized, open-label, treat-to-target, active-controlled trial. In this trial, patients were randomly assigned to either receive RYZODEG 70/30 once-daily administered at the main meal of the day and a mealtime insulin at remaining meals or another long-acting insulin once or twice daily combined with rapid-acting insulin at meals.

RYZODEG 70/30 administered once or twice daily with the main meal(s) in patients with type 2 diabetes when used with common oral anti-diabetic drugs was evaluated in four randomized, open-label, treat-to-target, active-controlled trials. In these trials, patients were randomized to RYZODEG 70/30 once-daily at breakfast or another long-acting or pre-mixed insulin once-daily according to approved labeling. Metformin, an oral medication, was given in both arms.

In each trial, the change in HbA1c from the start to finish of the trial was measured.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.